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Abstract Background Tauopathies, including Alzheimer’s disease, are characterized by the pathological aggregation of tau protein, which is strongly linked to dysregulation of the autophagy-lysosomal degradation pathway. However, therapeutic strategies targeting this pathway remain limited. Methods We used both in vitro and in vivo models to investigate the role of Raptor in tau pathology. Knockdown of Raptor was performed to assess its impact on mTORC1 activation, autophagy, and tau accumulation. The relationship between USP9X and Raptor was also examined. Pharmacological inhibition of USP9X with WP1130 was employed to further confirm the involvement of the USP9X-Raptor-mTORC1 axis in tau degradation. Results Elevated Raptor levels in the hippocampus of P301S mice led to hyperactivation of mTORC1, impairing autophagy flux. Knockdown of Raptor effectively suppressed mTORC1 activation, promoted autophagy, and mitigated the accumulation of tau and its phosphorylated isoforms. This reduction in tau pathology was accompanied by decreased neuronal loss in the hippocampus, amelioration of synaptic damage, and improvement in cognitive function. The increased Raptor protein observed in the hippocampus of P301S mice was likely attributable to elevated USP9X content, which enhanced Raptor deubiquitination and protected it from proteasomal degradation. Pharmacological inhibition of USP9X with WP1130 in vitro effectively suppressed Raptor, promoted autophagy, and accelerated the degradation of tau and phosphorylated tau. Conclusions Our findings highlight Raptor and USP9X as promising molecular targets for therapeutic intervention in tauopathies. Targeting the USP9X-Raptor-mTORC1 axis may provide a novel strategy for promoting autophagy and mitigating tau pathology in Alzheimer’s disease and other tauopathies. Graphical Abstract

Members of the genus Scaphanocephalus mature in accipitrids, particularly osprey, Pandion haliaetus, with metacercaria causing Black Spot Syndrome in reef fishes. In most of the world, only the type species, Scaphanocephalus expansus (Creplin, 1842) has been reported. Recent molecular studies in the Western Atlantic, Mediterranean and Persian Gulf reveal multiple species of Scaphanocephalus, but have relied on 28S rDNA, mainly from metacercariae, which limits both morphological identification and resolution of closely related species. Here we combine nuclear rDNA with mitochondrial sequences from adult worms collected in osprey across North America and the Caribbean to describe species and elucidate life cycles in Scaphanocephalus. A new species described herein can be distinguished from S. expansus based on overall body shape and size. Phylogenetic analysis of the whole mitochondrial genome of Scaphanocephalus indicates a close relationship with Cryptocotyle. We conclude that at least 3 species of Scaphanocephalus are present in the Americas and 2 others are in the Old World. Specimens in the Americas have similar or identical 28S to those in the Mediterranean and Persian Gulf, but amphi-Atlantic species are unlikely in light of divergence in cytochrome c oxidase I and the lack of amphi-Atlantic avian and fish hosts. Our results provide insight into the geographic distribution and taxonomy of a little-studied trematode recently linked to an emerging pathology in ecologically important reef fishes.

Abstract Understanding how human activities affect wildlife is fundamental for global biodiversity conservation. Ongoing land use change and human‐induced climate change, compel species to adapt their behaviour in response to shifts in their natural environments. Such responses include changes to a species' diet or trophic ecology, with implications for the wider ecosystem. This is particularly the case for predatory species or those that occupy high positions within trophic webs, such as raptors. Between 2002 and 2019, we observed 1578 feeding events of the globally near threatened and understudied, Red‐necked Falcon (Falco chicquera) in Bangladesh. We explored the effects of mean monthly temperature, precipitation, temperature differences, and urban land cover on (a) mean prey weights and (b) dietary composition of 15 falcon pairs. Falcons hunted smaller prey items during months with increased temperatures and precipitation, and in more urban areas. However, during months with increased temperature differences, falcons tended to prey on larger prey items. Being specialist aerial hunters, these dietary patterns were largely driven by the probabilities of bats and birds in the diet. Falcons were more likely to prey on bats during warmer and wetter months. Furthermore, urban pairs tended to prey on bats, whereas more rural pairs tended to prey on birds. Mean monthly temperature difference, i.e., a proxy for climate change, was better at explaining the probability of bats in the falcon diet than mean monthly temperature alone. Anthropogenic dietary shifts can have deleterious effects on species with declining populations or those of conservation concern. The effects of urbanisation and human‐induced climate change are expected to continue into the foreseeable future. Therefore, our findings represent a cornerstone in our understanding of how falcons respond to an increasingly human‐dominated world.

Raptors can change the shape and area of their wings to an exceptional degree in a fast and efficient manner, surpassing other birds, insects, or bats. Some researchers have focused on the functional properties of muscle skeletons, mechanics, and flapping robot design. However, the wing motion of the birds of prey has not been measured quantitatively, and synthetic bionic wings with morphing abilities similar to raptors are far from reality. Therefore, in the current study, a 3D suspension system for holding bird carcasses was designed and fabricated to fasten the wings of Falco Peregrinus with a series of morphing postures. Subsequently, the wing skeleton of the falcon was scanned during extending motions using the computed tomography (CT) approach to obtain three consecutive poses. Subsequently, the skeleton was reconstructed to identify the contribution of the forelimb bones to the extending/folding motions. Inspired by these findings, we propose a simple mechanical model with four bones to form a wing-morphing mechanism using the proposed pose optimisation method. Finally, a bionic wing mechanism was implemented to imitate the motion of the falcon wing—divided into inner and outer wings with folding and twisting motions. The results show that the proposed four-bar mechanism can track bone motion paths with high fidelity.

Abstract Background Natal dispersal, the distance between site of birth and site of first breeding, has a fundamental role in population dynamics and species’ responses to environmental changes. Population density is considered a key driver of natal dispersal. However, few studies have been able to examine densities at both the natal and the settlement site, which is critical for understanding the role of density in dispersal. Additionally, the role of density on natal dispersal remains poorly understood in long-lived and slowly reproducing species, due to their prolonged dispersal periods and often elusive nature. We studied the natal dispersal of the white-tailed eagle (Haliaeetus albicilla) in response to local breeder densities. We investigated the effects of the number of active territories around the natal site on (a) natal dispersal distance and (b) the difference between natal and settlement site breeder density. We were interested in whether eagles showed tendencies of conspecific attraction (positive density-dependence) or intraspecific competition (negative density-dependence) and how this related to settlement site breeder density. Methods We used a combination of long-term visual and genotypic identification to match individuals from their breeding site to their natal nest. We identified natal dispersal events for 355 individuals hatched between 1984 and 2015 in the Baltic Sea coast and Arctic areas of Finland. Of those, 251 were identified by their genotype. Results Individuals born in high-density areas dispersed shorter distances than those born in low-density areas, but settled at lower density breeding sites in comparison to their natal site. Eagles born in low natal area densities dispersed farther but settled in higher density breeding sites compared to their natal site. Conclusions We show that eagles might be attracted by conspecifics (positive density-dependence) to identify high-quality habitats or find mates, but do not settle in the most densely populated areas. This indicates that natal dispersal is affected by an interplay of conspecific attraction and intraspecific competition, which has implications for population dynamics of white-tailed eagles, but also other top predators. Furthermore, our study demonstrates the value of long-term collection of both nestling and (non-invasive) adult DNA samples, and thereafter using genotype matching to identify individuals in long-lived and elusive species.

Abstract Background mTORC1 (mechanistic target of rapamycin complex 1) is associated with lymphoma progression. Oncogenic RRAGC (Rag guanosine triphosphatase C) mutations identified in patients with follicular lymphoma facilitate the interaction between Raptor (regulatory protein associated with mTOR) and Rag GTPase. It promotes the activation of mTORC1 and accelerates lymphomagenesis. Cardamonin inhibits mTORC1 by decreasing the protein level of Raptor. In the present study, we investigated the inhibitory effect and possible mechanism of action of cardamonin in RRAGC-mutant lymphoma. This could provide a precise targeted therapy for lymphoma with RRAGC mutations. Methods Cell viability was measured using a cell counting kit-8 (CCK-8) assay. Protein expression and phosphorylation levels were determined using western blotting. The interactions of mTOR and Raptor with RagC were determined by co-immunoprecipitation. Cells overexpressing RagC wild-type (RagCWT) and RagC Thr90Asn (RagCT90N) were generated by lentiviral infection. Raptor knockdown was performed by lentivirus-mediated shRNA transduction. The in vivo anti-tumour effect of cardamonin was assessed in a xenograft model. Results Cardamonin disrupted mTOR complex interactions by decreasing Raptor protein levels. RagCT90N overexpression via lentiviral infection increased cell proliferation and mTORC1 activation. The viability and tumour growth rate of RagCT90N-mutant cells were more sensitive to cardamonin treatment than those of normal and RagCWT cells. Cardamonin also exhibited a stronger inhibitory effect on the phosphorylation of mTOR and p70 S6 kinase 1 in RagCT90N-mutant cells. Raptor knockdown abolishes the inhibitory effects of cardamonin on mTOR. An in vivo xenograft model demonstrated that the RagCT90N-mutant showed significantly higher sensitivity to cardamonin treatment. Conclusions Cardamonin exerts selective therapeutic effects on RagCT90N-mutant cells. Cardamonin can serve as a drug for individualised therapy for follicular lymphoma with RRAGC mutations.

Satellite tracking allows for novel investigations into golden eagle home range characteristics. Understanding home range characteristics is important for conservation and for assessing the potential impact of landscape changes from forest planting, wind farms, etc. Small sample sizes, inconsistent definitions and methods restricted several previous studies. Our study involved 69 resident tagged eagles with over one year of data across five Scottish regions. Home range size was estimated from 95% isopleth contours extracted from Utilisation Distributions. Above a small threshold, estimated range size was not affected by the number of records but at least one year of data is required, largely because of the breeding and non-breeding seasonal differences. There were no significant range size differences between birds tagged as range holders and those previously tagged as nestlings. Across four regions, with considerable intra-regional variation, planar 95% isopleths did not differ (medians, km2): Argyll 58.9, Northwest Highlands 61.7, Northeast Highlands 89.3, South of Scotland 91.9. Ranges in the isolated Outer Hebrides region were exceptionally small, at 24.0 km2. Estimated range area was usually reduced to 70–80% of the planar area when restricted to usable habitat, as estimated by the Golden Eagle Topography (GET) model. Applying measures of known unsuitable habitat (closed-canopy commercial forest and wind turbines) further reduced usable open land. Loss of otherwise suitable habitat was substantially due to commercial forest. Larger ranges had larger extents of suitable habitat (according to GET), with no apparent optimum of preferred GET habitat. Range size was not different across a year between the sexes. Breeding ranges were smaller, and females’ breeding ranges were much smaller than those of males, but larger than males’ ranges in the non-breeding season. Breeding attempt duration was probably also influential. Our study provides novel insights into golden eagle home range characteristics and can guide further research and practical applications.

The first breeding of osprey (Pandion haliaetus) on Jeju Island, South Korea, were observed in 2015, and ospreys bred on three sites. We found a total of three nests and observed that A site nest bred on successfully from 2017 to 2020. The number of eggs per clutch ranged from two to four, with a mean ± SD of 3.16 ± 0.75. The nesting period varied from 71 days to 79 days, with an average duration of 76.2 ± 3.18 days. The incubation period ranged from 34 days to 38 days, averaging 35.8 ± 1.72 days. Fledging dates ranged from July 4th to 13th. The nest tree species was Pinus thunbergii, and the average tree height was 16.2 ± 3.12 m. On average, the nest height from the ground was 14.8 ± 2.57 m. The average diameter at breast height of the nesting trees was 36.1 ± 2.02 cm. Of the total 19 eggs produced, the hatching rate was 91.4% ± 10.2%, fledgling rate was 68.6% ± 26.9%, and breeding success was 65.6% ± 25.1%. Little ecological information is available on osprey living in South Korea; therefore, this study makes a meaningful contribution to provide baseline ecological data from South Korea for this species.

The canonical target of the glucagon-like peptide-1 receptor (GLP-1R), Protein Kinase A (PKA), has been shown to stimulate mechanistic Target of Rapamycin Complex 1 (mTORC1) by phosphorylating the mTOR-regulating protein Raptor at Ser791 following β-adrenergic stimulation. The objective of these studies is to test whether GLP-1R agonists similarly stimulate mTORC1 via PKA phosphorylation of Raptor at Ser791 and whether this contributes to the weight loss effect of the therapeutic GLP-1R agonist liraglutide. We measured phosphorylation of the mTORC1 signaling target ribosomal protein S6 in Chinese Hamster Ovary cells expressing GLP-1R (CHO-Glp1r) treated with liraglutide in combination with PKA inhibitors. We also assessed liraglutide-mediated phosphorylation of the PKA substrate RRXS*/T* motif in CHO-Glp1r cells expressing Myc-tagged wild-type (WT) Raptor or a PKA-resistant (Ser791Ala) Raptor mutant. Finally, we measured the body weight response to liraglutide in WT mice and mice with a targeted knock-in of PKA-resistant Ser791Ala Raptor. Liraglutide increased phosphorylation of S6 and the PKA motif in WT Raptor in a PKA-dependent manner but failed to stimulate phosphorylation of the PKA motif in Ser791Ala Raptor in CHO-Glp1r cells. Lean Ser791Ala Raptor knock-in mice were resistant to liraglutide-induced weight loss but not setmelanotide-induced (melanocortin-4 receptor-dependent) weight loss. Diet-induced obese Ser791Ala Raptor knock-in mice were not resistant to liraglutide-induced weight loss; however, there was weight-dependent variation such that there was a tendency for obese Ser791Ala Raptor knock-in mice of lower relative body weight to be resistant to liraglutide-induced weight loss compared to weight-matched controls. Together, these findings suggest that PKA-mediated phosphorylation of Raptor at Ser791 contributes to liraglutide-induced weight loss.

Humans have shot raptors for centuries. However, in many countries these actions have been illegal since the mid-twentieth century. Despite this history, there is not a comprehensive understanding of the characteristics of this activity, its frequency, and why it occurs. We used literature review and principles drawn from ecology, sociology, and criminology to understand this problem. First, we review literature on raptor shooting globally to explore documented motivations for shooting and we describe the history of raptor shooting in the United States of America (USA). Then, to illustrate the contemporary frequency and geographic breadth of the shooting of raptors, we systematically compile records from scientific and media reports from across the USA. Finally, we outline a transdisciplinary framework to meet the challenge of understanding and managing illegal shooting of raptors. Our framework encompasses six best practices: (1) understand the biology of the problem, (2) build professional networks and partnerships, (3) leverage engagement and public support, (4) apply insights from study of human-wildlife interactions, (5) draw lessons from criminology, and (6) use implementation science to evaluate outcomes. We illustrate application of these best practices with a case study from an Illegal Shooting Working Group recently formed in Boise, Idaho, USA. There is growing recognition that illegal shooting of raptors is a pressing conservation challenge. Solving this challenge can be facilitated by inclusion of information from multiple fields of study; the approach we outline provides one potential mechanism to address this issue.

Objective: The essential role of raptor/mTORC1 signaling in β-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the role of mTORC1 function in adaptation of β-cells to insulin resistant state. Method: Here, we use mice with heterozygous deletion of raptor in β-cells (βraHet) to assess whether reduced mTORC1 function is critical for β-cell function in normal conditions or during β-cell adaptation to high-fat diet (HFD). Results: Deletion of a raptor allele in β-cells showed no differences at the metabolic level, islets morphology, or β-cell function in mice fed regular chow. Surprisingly, deletion of only one allele of raptor increases apoptosis without altering proliferation rate and is sufficient to impair insulin secretion when fed a HFD. This is accompanied by reduced levels of critical β-cell genes like Ins1, MafA, Ucn3, Glut2, Glp1r, and specially PDX1 suggesting an improper β-cell adaptation to HFD. Conclusion: This study identifies that raptor levels play a key role in maintaining PDX1 levels and β-cell function during the adaptation of β-cell to HFD. Finally, we identified that Raptor levels regulate PDX1 levels and β-cell function during β-cell adaptation to HFD by reduction of the mTORC1-mediated negative feedback and activation of the AKT/FOXA2/PDX1 axis. We suggest that Raptor levels are critical to maintaining PDX1 levels and β-cell function in conditions of insulin resistance in male mice.

Abstract Background A high prevalence of parasites may result from life-long persistence of infection or from high reinfection rates. We have studied blood parasites in a breeding population of the accipitrid raptor, Eurasian sparrowhawk (Accipiter nisus), to determine parasite diversity and turnover. Methods During this 7-year study, 210 adult Eurasian sparrowhawks breeding in the city of Prague were checked for parasites using several diagnostic methods. Results In both female and male raptors, parasites of the genus Leucocytozoon were the most prevalent (92% and 85%, respectively) followed in decreasing order of prevalence by those of genus Trypanosoma (74% and 68%, respectively) and genus Haemoproteus (46% and 16%, respectively). The prevalence of all parasites increased with age in both sexes, with the females at each respective age having the higher prevalence. There was a positive association between Haemoproteus and Leucocytozoon infections. Persistence at the individual level was higher than incidence for Trypanosoma and Haemoproteus. In the case of Leucocytozoon and Trypanosoma, most individuals probably become infected in their first year of life or even before dispersal from the nest. The detected parasites belonged to Trypanosoma avium sensu stricto, Leucocytozoon sp. (haplotypes ACNI1 and ACNI3) and Leucocytozoon mathisi (haplotype ACNI4) and two new lineages of the Haemoproteus elani complex (ACCNIS6 and ACCNIS7). Detailed analysis of parasite lineages in individuals that were repeatedly sampled revealed lineage turnover that would otherwise remain hidden. Phylogenetic analysis revealed that the detected Haemoproteus belongs to a phylogenetically distant group whose taxonomic position requires further analysis. Conclusions All three genera of blood parasites persist in infected individuals, thus enabling sustainability of vector transmission cycles. Prevalence increases with age; however, there is a high turnover of Leucocytozoon lineages. No clear evidence of parasite-induced mortality was found, and most of the individuals were infected early in life, particularly in the case of Leucocytozoon. Graphical abstract

Abstract Somatostatin-expressing interneurons (SOM-INs) are a major subpopulation of GABAergic cells in CA1 hippocampus that receive excitation from pyramidal cells (PCs) and provide feedback control of synaptic inputs onto PC dendrites. Excitatory synapses from PCs onto SOM-INs (PC-SOM synapses) exhibit long-term potentiation (LTP) mediated by type 1a metabotropic glutamate receptors (mGluR1a). LTP at PC-SOM synapses translates in lasting regulation of metaplasticity of entorhinal and CA3 synaptic inputs on PCs and contributes to hippocampus-dependent learning. A persistent form of PC-SOM synapse LTP lasting hours is prevented by blockers of transcription and translation, and a more transient form of PC-SOM synapse LTP lasting tens of minutes requires mTORC1-signaling, suggesting an involvement of protein synthesis. However, the role of protein synthesis in these forms of plasticity has not been directly demonstrated. Here we use the SUrface SEnsing of Translation (SUnSET) assay of protein synthesis to directly show that the induction protocols for both forms of LTP at PC-SOM synapses stimulate protein synthesis in SOM-INs. Moreover, protein synthesis stimulated by persistent LTP induction was prevented in mice with a SOM-IN conditional knock-out of Raptor, an essential component of mTORC1, indicating a critical role of mTORC1 in the control of translation in PC-SOM synapse plasticity. Moreover, protein synthesis induced by both forms of LTP may share common mechanisms as transient LTP induction occluded further stimulation of protein synthesis by persistent LTP induction. Our findings highlight a crucial role of protein synthesis and its control by mTORC1 in SOM-INs that is important for hippocampus-dependent memory function.

Gut microbiota are increasingly recognized as important drivers of host health and fitness across vertebrate taxa. Given that gut microbial composition is directly influenced by the environment, gut microbiota may also serve as an eco‐physiological mechanism connecting host ecology, such as diet, and physiology. Although gut microbiota have been well‐studied in mammalian systems, little is known about how gut microbial diversity and composition impact morphological and physiological development in wild birds. Here, we characterized both diet and gut microbial diversity of free‐living American kestrel Falco sparverius nestlings throughout development to test whether gut microbial diversity predicts host morphological and physiological traits in either contemporary or time‐lagged manners. Gut microbial alpha diversity on day 21 of nestling development was positively correlated with diet alpha diversity representative of the majority of nestling development (days 5–20). Gut microbial alpha diversity early in development was negatively correlated with body mass in both contemporary and time‐lagged manners. Gut microbial alpha diversity early in development was positively correlated with blood glucose later in development. As nestlings experience rapid growth demands in preparation to fledge, these time‐lagged associations may indicate that gut microbial diversity at early critical developmental windows may determine the future trajectory of morphological and physiological traits underlying metabolism that ultimately impact fitness.

Objective: Obesity is a complex disorder and is linked to chronic diseases such as type 2 diabetes. Major intrinsically disordered NOTCH2-associated receptor2 (MINAR2) is an understudied protein with an unknown role in obesity and metabolism. The purpose of this study was to determine the impact of Minar2 on adipose tissues and obesity. Method: We generated Minar2 knockout (KO) mice and used various molecular, proteomic, biochemical, histopathology, and cell culture studies to determine the pathophysiological role of Minar2 in adipocytes. Results: We demonstrated that the inactivation of Minar2 results in increased body fat with hypertrophic adipocytes. Minar2 KO mice on a high-fat diet develop obesity and impaired glucose tolerance and metabolism. Mechanistically, Minar2 interacts with Raptor, a specific and essential component of mammalian TOR complex 1 (mTORC1) and inhibits mTOR activation. mTOR is hyperactivated in the adipocytes deficient for Minar2 and over-expression of Minar2 in HEK-293 cells inhibited mTOR activation and phosphorylation of mTORC1 substrates, including S6 kinase, and 4E-BP1. Conclusion: Our findings identified Minar2 as a novel physiological negative regulator of mTORC1 with a key role in obesity and metabolic disorders. Impaired expression or activation of MINAR2 could lead to obesity and obesity-associated diseases.

Background A balance on nutrient supply and redox homeostasis is required for cell survival, and increased antioxidant capacity of cancer cells may lead to chemotherapy failure. Objective To investigate the mechanism of anti-proliferation of cardamonin by inducing oxidative stress in ovarian cancer cells. Methods After 24 h of drug treatment, CCK8 kit and wound healing test were used to detect cell viability and migration ability, respectively, and the ROS levels were detected by flow cytometry. The differential protein expression after cardamonin administration was analyzed by proteomics, and the protein level was detected by Western blotting. Results Cardamonin inhibited the cell growth, which was related to ROS accumulation. Proteomic analysis suggested that MAPK pathway might be involved in cardamonin-induced oxidative stress. Western blotting showed that cardamonin decreased Raptor expression and the activity of mTORC1 and ERK1/2. Same results were observed in Raptor KO cells. Notably, in Raptor KO cells, the effect of cardamonin was weakened. Conclusion Raptor mediated the function of cardamonin on cellular redox homeostasis and cell proliferation through mTORC1 and ERK1/2 pathways.

Wind power is commonly used to reduce greenhouse gas emissions but often has negative effects on biodiversity. In this study, I investigated the effects of wind farm and power line construction on the territory status of the Eurasian goshawk Accipiter gentilis, whether fledglings were produced or not, and the number of fledglings. Included were 55 goshawk territories investigated before and after the construction period. I found that the territory status declined significantly in the influence area within 3 km from the disturbance compared to the control area more than 7 km away. Interestingly, the decline in territory status was similar in the distance categories 0–1 km, 1–2 km, and 2–3 km, while there was nearly no change in territory status in the control area, thus indicating that the influence area from this kind of disturbance was minimum 3 km from the nest. The number of breeding pairs declined significantly during the construction period only in the influence area. Possible reasons might be higher mortality caused by collisions with power lines, desertion, avoidance of the areas with noise and disturbance from the constructions, and possible indirect effects caused by reductions in prey species. I found no effects of the construction on the number of fledglings.

Despite advancements through satellite telemetry, knowledge of the behaviour and ecology of large raptors during natal dispersal is still poor, even though this transience phase is important in understanding the population dynamics and conservation of these keystone species. After this phase, which can take several years, the subsequent rapid transitional event on first territory settlement is less studied. It apparently occurs earlier without competition from existing territory occupants. The time of year when young large raptors settle on a territory has rarely been addressed empirically. Our study of seasonal timing of first settlement used data from 46 golden eagles GPS-tagged as nestlings in Scotland which were tracked to their first territory settlement, as adjudged by a robust algorithmic method. We show that when young golden eagles occupied their first territory, their settlements were uncommon in summer and most common in late winter/spring, but also occurred in autumn into early winter. The significant seasonal pattern was consistent, regardless of the probable prior occupancy status (vacant/occupied) of the settled territory (respectively, the likely absence or presence of defending territorial birds). This showed that seasonal territory settlement was unlikely to be related to any response from territory occupants. It infers further that seasonality in first territory settlement was underpinned by innate behaviours in dispersing eagles. Seasonal distribution of settlement dates was significantly different between sexes, with males more likely to settle in autumn, predominantly in prior vacant territories. We speculate on potential causative drivers behind our results and conclude that more research is clearly needed in this field of study.

Understanding drivers underlying birds’ responses to operational wind turbines is essential for robust wind farm proposal assessments, especially for large raptors with life history traits engendering sensitivity to impacts from two potential adverse effects: fatality through collision with rotating turbine blades and functional habitat loss through avoidance of turbines. The balance between these two potential effects represents opposing extremes on a continuum and is influenced by several factors. Collisions have an obvious impact on survival, but the impacts of avoidance may be more insidious and potentially more significant for a population. It is reasonable to conclude that collisions are less likely when blades are motionless. Consequently, turbine shutdown systems (TSSs, “shutdown on demand” or “curtailment”), instigated as raptors approach operational turbines, may provide mitigation against collisions. By contrast, if avoidance is most likely, this could be independent of blade motion, and TSSs/curtailment would provide no mitigation against habitat loss. For birds tending to wariness of turbines, therefore, it is important to understand if it is conditional on blade motion. Scottish golden eagles show a strong propensity to avoid (be wary of) turbines, subject largely to the suitability of habitat at and surrounding turbine locations. A previous Scottish study found that approach distances to turbines by non-territorial eagles were unaffected by blade motion but were closer at higher wind speed. Here, we analyse movement data from a GPS-tagged territorial eagle and non-territorial eagles responding to the motion status (and wind speed) of turbines at another Scottish wind farm. Eagles’ approach distances to turbines were only weakly affected by blade motion but were closer at higher wind speed. We again found that habitat suitability in and around turbine locations was strongly influential on eagles’ approach distance to turbines. Our confirmation that blade motion had little effect on Scottish golden eagles’ wariness of turbines suggests that for eagles that are prone to avoid turbines, their wariness is a response to turbines per se, and not blades’ movement. In our study system, and others where avoidance is the predominant response, curtailment of turbines’ operation on birds’ close approaches, or making turbine blades more obvious, should, therefore, have little material influence on functional habitat loss impacts. If true, this has important implications for wind farm designs and any proposed mitigation.

Raptor, a key component of mTORC1, is required for recruiting substrates to mTORC1 and contributing to its subcellular localization. Raptor has a highly conserved N-terminus domain and seven WD40 repeats, which interact with mTOR and other mTORC1-related proteins. mTORC1 participates in various cellular events and mediates differentiation and metabolism. Directly or indirectly, many factors mediate the differentiation and function of lymphocytes that is essential for immunity. In this review, we summarize the role of Raptor in lymphocytes differentiation and function, whereby Raptor mediates the secretion of cytokines to induce early lymphocyte metabolism, development, proliferation and migration. Additionally, Raptor regulates the function of lymphocytes by regulating their steady-state maintenance and activation.

Outbreaks of neurological disease associated with Sarcocystis calchasi have been observed in captive and free-ranging rock pigeons (Columba livia) in Europe and the United States as well as in wild Brandt's cormorants (Phalacrocorax penicillatus) and captive psittacines in California, USA. Experimental and field studies have identified northern goshawks (Accipiter gentilis) and European sparrowhawks (A. nisus) as definitive hosts in Europe while the definitive hosts elsewhere remain unknown. In this study, we aimed to identify the potential definitive host(s) of S. calchasi through molecular analysis of intestinal samples from seven predatory (n = 85) and one omnivorous (n = 11) bird species in California. In total, apicomplexan-generic 28S rRNA PCR products were obtained and sequenced for 42 raptors. Three of 16 (18.8%) Cooper's hawks (A. cooperii) and two of 26 (5.6%) red-tailed hawks (Buteo jamaicensis) also tested positive for the S. calchasi-specific ITS1 PCR and sequencing of the 28S rRNA PCR product was 100% homologous to S. calchasi. In addition to S. calchasi (5.9%; 5/85), other Sarcocystis spp. detected in raptors included: S. jamaicensis (21.2%; 18/85), S. columbae (8.2%; 7/85), S. turdusi (7.1%; 6/85), and S. halieti (4.7; 4/85%). Infections with closely related S. jamaicensis and S. (Frenkelia) microti (9.4%; 8/85) could not be distinguished for eight raptors. Eumonospora henryae (1.2%; 1/85) was detected in one raptor. Our results indicate for the first time that S. calchasi may have a definitive host range in North America that includes at least two raptors, Cooper's hawks and red-tailed hawks, within the family Accipitridae.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality. Human phenylalanine tRNA synthetase (PheRS) comprises two α catalytic subunits encoded by the FARSA gene and two β regulatory subunits encoded by the FARSB gene. FARSB is a potential oncogene, but no experimental data show the relationship between FARSB and HCC progression. We found that the high expression of FARSB in liver cancer is closely related to patients’ low survival and poor prognosis. In liver cancer cells, the mRNA and protein expression levels of FARSB are increased and promote cell proliferation and migration. Mechanistically, FARSB activates the mTOR complex 1 (mTORC1) signaling pathway by binding to the component Raptor of the mTORC1 complex to play a role in promoting cancer. In addition, we found that FARSB can inhibit erastin-induced ferroptosis by regulating the mTOR signaling pathway, which may be another mechanism by which FARSB promotes HCC progression. In summary, FARSB promotes HCC progression and is associated with the poor prognosis of patients. FARSB is expected to be a biomarker for early screening and treatment of HCC.

Hypothalamic mTORC1 signaling is involved in nutrient sensing. Neurons that express the agouti-related protein (AgRP) are activated by food restriction and integrate interoceptive and exteroceptive signals to control food intake, energy expenditure, and other metabolic responses. To determine whether mTORC1 signaling in AgRP neurons is necessary for regulating energy and glucose homeostasis, especially in situations of negative energy balance, mice carrying ablation of the Raptor gene exclusively in AgRP-expressing cells were generated. AgRPΔRaptor mice showed no differences in body weight, fat mass, food intake, or energy expenditure; however, a slight improvement in glucose homeostasis was observed compared to the control group. When subjected to 5 days of food restriction (40% basal intake), AgRPΔRaptor female mice lost less lean body mass and showed a blunted reduction in energy expenditure, whereas AgRPΔRaptor male mice maintained a higher energy expenditure compared to control mice during the food restriction and 5 days of refeeding period. AgRPΔRaptor female mice did not exhibit the food restriction-induced increase in serum corticosterone levels. Finally, although hypothalamic fasting- or refeeding-induced Fos expression showed no differences between the groups, AgRPΔRaptor mice displayed increased hyperphagia during refeeding. Thus, some metabolic and neuroendocrine responses to food restriction are disturbed in AgRPΔRaptor mice.

Abstract Background Cancer‐related muscle wasting occurs in most cancer patients. An important regulator of adult muscle mass and function is the Akt–mTORC1 pathway. While Akt–mTORC1 signalling is important for adult muscle homeostasis, it is also a major target of numerous cancer treatments. Which role Akt–mTORC1 signalling plays during cancer cachexia in muscle is currently not known. Here, we aimed to determine how activation or inactivation of the pathway affects skeletal muscle during cancer cachexia. Methods We used inducible, muscle‐specific Raptor ko (mTORC1) mice to determine the effect of reduced mTOR signalling during cancer cachexia. On the contrary, in order to understand if skeletal muscles maintain their anabolic capacity and if activation of Akt–mTORC1 signalling can reverse cancer cachexia, we generated mice in which we can inducibly activate Akt specifically in skeletal muscles. Results We found that mTORC1 signalling is impaired during cancer cachexia, using the Lewis lung carcinoma and C26 colon cancer model, and is accompanied by a reduction in protein synthesis rates of 57% (P 0.001), but does not further increase muscle wasting. On the other hand, activation of Akt–mTORC1 signalling in already cachectic animals completely reverses the 15–20% loss in muscle mass and force (P

Large scavengers are strongly dependent on environmental conditions and carrion distribution and abundance, so season and breeding-related factors may influence the spatial ecology of species such as the Cinereous Vulture (Aegypius monachus), the largest European raptor. Iberia holds one of the biggest populations worldwide, but some aspects of the spatial ecology of the species in this region remain unknown. In this study, 17 adult Cinereous Vultures were GPS-tracked in order to study their spatial ecology during the adult phase. The average monthly home ranges (95% Kernel Density Estimation, KDE) and core areas (50% KDE) were 6543 ​± ​19,935 ​km2 and 1174 ​± ​4004 ​km2, respectively. The average monthly home range fidelity ranged between 50 and 73%. Differences in movement-related variables between the seasonal periods (incubation, chick-rearing and non-breeding) were found. During the chick-rearing period, the monthly accumulated distance was higher than during the other periods: 3316 ​± ​1108 (chick-rearing) vs. 1621 ​± ​622 (incubation) vs. 1726 ​± ​1159 ​km per month (non-breeding). Additionally, large home range sizes were more frequent during the chick-rearing period. There are two likely causes for these seasonal differences. Firstly, chick-rearing entails a higher energetic expenditure by the parental individuals in foraging activities, so larger movements and foraging areas are expected during this period. Secondly, the flight is favoured during spring and summer due to environmental conditions. Matching chick-rearing and warm months is a great evolutionary advantage for soaring-gliding raptors, as it allows them to cover larger areas with low energy expenditure. Furthermore, six individuals tagged as nestlings highlight the philopatric behaviour of the species: vultures settle their breeding areas 54 ​± ​51 ​km from their natal nest (range ​= ​9–138 ​km).

The diets of raptors are some of the best studied and well-known of all bird groups. Raptors are typically carnivores, hunting and feeding on vertebrates and, for some species, invertebrates. Here, we described instances of the Black Kite (Milvus migrans) and Whistling Kite (Haliastur sphenurus) consuming non-native avocado (Persea americana) fruit in commercial orchards in northern Australia, over multiple years. This appears to be the first instance of frugivory by raptors in Australia. We review instances of frugivory for other raptor species globally. This review finds that 29 species of raptor from the families Falconidae, Accipitridae and Cathartidae have been recorded consuming fruit, significantly more than previous reviews.

Bird and bat turbine collision fatalities are a principal biodiversity impact at wind energy facilities. Raptors are a group at particular risk and often the focus of post-construction fatality monitoring programs. To estimate fatalities from detected carcasses requires correction for biases, including for carcasses that are removed or decompose before the following search. This is addressed through persistence trials, where carcasses are monitored until no longer detectable or the trial ends. Sourcing sufficient raptor carcasses for trials is challenging and surrogates that are typically used often have shorter persistence times than raptors. We collated information from raptor carcass persistence trials to evaluate consistencies between trials and assess the implications of using persistence values from other studies in wind facility fatality estimates. We compiled individual raptor carcass persistence times from published sources along with information on methods and location, estimated carcass persistence using GenEst and ran full fatality estimates using the carcass persistence estimates and mock datasets for other information. We compiled results from 22 trials from 17 sites across four terrestrial biomes, with trials lasting between 7 and 365 days and involving between 11 and 115 carcasses. Median carcass persistence was estimated at 420 days (90% confidence interval (CI) of 290 to 607 days) for the full dataset. Persistence time varied significantly between trials (trial-specific persistence estimates of 14 (5–42) days to 1,586 (816–3,084) days) but not between terrestrial biomes. We also found no significant relationship between either the number of carcasses in the trial or trial duration and estimated carcass persistence. Using a mock dataset with 12 observed fatalities, we estimated annual fatalities of 25 (16–33) or 26 (17–36) individuals using a 14- or 28-day search interval respectively using global dataset. When using trial-specific carcass persistence estimates and the same mock dataset, estimated annual fatalities ranged from 22 (14–30) to 37 (21–63) individuals for a 14-day search interval, and from 22 (15–31) to 47 (26–84) individuals for a 28-day search interval. The different raptor carcass persistence rates between trials translated to small effects on fatality estimates when using recommended search frequencies, since persistence rates were generally much longer than the search interval. When threatened raptor species, or raptors of particular concern to stakeholders are present, and no site-specific carcass persistence estimates are available, projects should use the lowest median carcass persistence estimate from this study to provide precautionary estimates of fatalities. At sites without threatened species, or where the risk of collision to raptors is low, the global median carcass persistence estimate from this review could be used to provide a plausible estimate for annual raptor fatalities.

Bcl-3 is an atypical IκB family member that regulates transcription in the nucleus by binding to the p50/p52 homologous dimer subunit. Although various studies illustrate the important role of Bcl-3 in physiological function, its role in metabolism is still unclear. We found that Bcl-3 has a metabolic regulatory effect on autoimmunity. Bcl-3-depleted mice are unable to develop experimental autoimmune encephalomyelitis. The disease resistance was linked to an increase in lactate levels in Th17 cells, and lactate could alleviate EAE development in WT mice. Bcl-3 deficient mice had more differentiated Th17 cells and an increased extracellular acidification rate in these cells. Concurrently, their ultimate respiration rate and respiratory reserve capacity were significantly lower than wild-type mice. However, adding GNE-140 (LADH inhibitor) to Bcl-3-deficient Th17 cells could reverse the phenomenon, and lactate supplementation could increase the glycolysis metabolism of Th17 cells in WT mice. Mechanically, Bcl-3 could interact with Raptor through ANK and RNC domains. Therefore, Bcl-3 regulates Th17 pathogenicity by promoting Raptor mediated energy metabolism, revealing a novel regulation of adaptive immunity.

Research on potentially adverse effects of wind farms is an expanding field of study and often focuses on large raptors, such as golden eagles, largely because of their life history traits and extensive habitat requirements. These features render them sensitive to either fatality (collision with turbine blades) or functional habitat loss (avoidance through wariness of turbines). Simplistically, avoidance is antagonistic to collision; although, the two processes are not necessarily mutually exclusive in risk. A bird that does not enter a wind farm or avoids flying close to turbines cannot collide with a blade and be killed. In the USA, collision fatality is implicated as the typical adverse effect. In Scotland, avoidance of functional habitat loss appears more likely, but this depends in part on the habitat suitability of turbine locations. Previous Scottish studies have largely concentrated on the responses of GPS-tagged non-territorial golden eagles during dispersal. Several arguments predict that territorial eagles may have lower avoidance (be less wary) of turbines than non-territorial birds. Hence, we contrasted the responses of GPS-tagged non-territorial (intruding) and territorial eagles to the same turbines at 11 operational Scottish wind farms. We show that territorial eagles rarely approached turbines, but, as in previous Scottish studies of non-territorial birds, the spatial extent of avoidance depended on the habitat suitability of both turbine locations and their wider surroundings. Unexpectedly, we found that territorial eagles were apparently as wary as intruding non-territorial conspecifics of the same turbines. Our results show that regardless of age or territorial status, Scottish golden eagles largely avoided wind turbine locations, but this avoidance was conditional, in part, on where those turbines were located. Responses to turbines were also strongly dependent on birds’ identities and different wind farms. We speculate on how widespread our findings of avoidance of turbines by golden eagles are elsewhere in Europe, where there appear to be no published studies showing the level of collision fatalities documented in the USA.

The mechanistic target of rapamycin (mTOR) kinase is a central regulator of cell growth and metabolism. It is the catalytic subunit of two distinct large protein complexes, mTOR complex 1 (mTORC1) and mTORC2. mTOR activity is subjected to tight regulation in response to external nutrition and growth factor stimulation. As an important mechanism of signaling transduction, the ‘second messenger’ cyclic nucleotides including cAMP and cGMP and their associated cyclic nucleotide-dependent kinases, including protein kinase A (PKA) and protein kinase G (PKG), play essential roles in mediating the intracellular action of a variety of hormones and neurotransmitters. They have also emerged as important regulators of mTOR signaling in various physiological and disease conditions. However, the mechanism by which cAMP and cGMP regulate mTOR activity is not completely understood. In this review, we will summarize the earlier work establishing the ability of cAMP to dampen mTORC1 activation in response to insulin and growth factors and then discuss our recent findings demonstrating the regulation of mTOR signaling by the PKA- and PKG-dependent signaling pathways. This signaling framework represents a new non-canonical regulation of mTOR activity that is independent of AKT and could be a novel mechanism underpinning the action of a variety of G protein-coupled receptors that are linked to the mTOR signaling network. We will further review the implications of these signaling events in the context of cardiometabolic disease, such as obesity, non-alcoholic fatty liver disease, and cardiac remodeling. The metabolic and cardiac phenotypes of mouse models with targeted deletion of Raptor and Rictor, the two essential components for mTORC1 and mTORC2, will be summarized and discussed.

Abstract Background Diet analysis is essential to understanding the functional role of large bird species in food webs. Morphological analysis of regurgitated bird pellet contents is time intensive and may underestimate biodiversity. DNA metabarcoding has the ability to circumvent these issues, but has yet to be done. Methods We present a pilot study using DNA metabarcoding of MT-RNR1 and MT-CO1 markers to determine the species of origin and prey of 45 pellets collected in Qinghai and Gansu Provinces, China. Results We detected four raptor species [Eurasian Eagle Owl (Bubo bubo), Saker Falcon (Falco cherrug), Steppe Eagle (Aquila nipalensis), and Upland Buzzard (Buteo hemilasius)] and 11 unique prey species across 10 families and 4 classes. Mammals were the greatest detected prey class with Plateau Pika (Ochotona curzoniae) being the most frequent. Observed Shannon’s and Simpson’s diversity for Upland Buzzard were 1.089 and 0.479, respectively, while expected values were 1.312 ± 0.266 and 0.485 ± 0.086. For Eurasian Eagle Owl, observed values were 1.202 and 0.565, while expected values were 1.502 ± 0.340 and 0.580 ± 0.114. Interspecific dietary niche partitioning between the two species was not detected. Conclusions Our results demonstrate successful use of DNA metabarcoding for understanding diet via a novel noninvasive sample type to identify common and uncommon species. More work is needed to understand how raptor diets vary locally, and the mechanisms that enable exploitation of similar dietary resources. This approach has wide ranging applicability to other birds of prey, and demonstrates the power of using DNA metabarcoding to study species noninvasively.

Abstract Background Core landbirds undergo adaptive radiation with different ecological niches, but the genomic bases that underlie their ecological diversification remain unclear. Results Here we used the genome-wide target enrichment sequencing of the genes related to vision, hearing, language, temperature sensation, beak shape, taste transduction, and carbohydrate, protein and fat digestion and absorption to examine the genomic bases underlying their ecological diversification. Our comparative molecular phyloecological analyses show that different core landbirds present adaptive enhancement in different aspects, and two general patterns emerge. First, all three raptorial birds (Accipitriformes, Strigiformes, and Falconiformes) show a convergent adaptive enhancement for fat digestion and absorption, while non-raptorial birds tend to exhibit a promoted capability for protein and carbohydrate digestion and absorption. Using this as a molecular marker, our results show relatively strong support for the raptorial lifestyle of the common ancestor of core landbirds, consequently suggesting a single origin of raptors, followed by two secondary losses of raptorial lifestyle within core landbirds. In addition to the dietary niche, we find at temporal niche that diurnal birds tend to exhibit an adaptive enhancement in bright-light vision, while nocturnal birds show an increased adaption in dim-light vision, in line with previous findings. Conclusions Our molecular phyloecological study reveals the genome-wide adaptive differentiations underlying the ecological diversification of core landbirds.

Hematopoietic stem cells (HSCs) ensure the lifelong production of blood cells throughout a lifetime. Latexin (Lxn) is thought to have a tumor suppressor role and endogenously down-regulate the number of HSCs via increased apoptosis. Therewithal, Raptor, and Rictor are components of the mammalian target of rapamycin complex-1, and 2 (mTORC), which are the regulatory structures for cell growth. However, Lxn, Raptor, and Rictor-associated molecular mechanisms underlying leukemia-induced HSCs proliferation are largely unknown. Nowadays, chronic lymphocytic leukemia (CLL) remains the most common leukemia type in adults. Therefore, we investigated the serum levels of Lxn, Raptor, and Rictor in CLL patients. We randomized 40 patients with newly diagnosed, untreated CLL. Serum levels of Lxn, Raptor, and Rictor were examined using ELISA assay. The results showed that serum Lxn levels reduced in patients with CLL. Moreover, the Rictor level increased in association with the up-regulation of leukocytosis. Although there was a tendency for an increase of the Raptor levels, the differences did not reach statistical significance. The up-regulated Raptor and Rictor levels in CLL suggested that it was associated with cancer pathogenesis. However, decreased Lxn levels raised the question of whether the disease is secondary to epigenetic features or if it is caused by pathology related to Lxn. The negative correlation between Lxn and Raptor/Rictor levels can provide new methods for the treatment of CLL, which are likely to increase the quality of life and improve the prognosis of the disease. In conclusion, further clinical studies are needed to elucidate the role of Lxn and Raptor/Rictor with the newly defined molecular properties in hematological malignancies and the clinical implications of their use. [Med-Science 2021; 10(2.000): 511-5]

The mTOR pathway is an essential regulator of cell growth and metabolism. Midbrain dopamine neurons are particularly sensitive to mTOR signaling status as activation or inhibition of mTOR alters their morphology and physiology. mTOR exists in two distinct multiprotein complexes termed mTORC1 and mTORC2. How each of these complexes affect dopamine neuron properties, and whether they have similar or distinct functions is unknown. Here, we investigated this in mice with dopamine neuron-specific deletion of Rptor or Rictor, which encode obligatory components of mTORC1 or mTORC2, respectively. We find that inhibition of mTORC1 strongly and broadly impacts dopamine neuron structure and function causing somatodendritic and axonal hypotrophy, increased intrinsic excitability, decreased dopamine production, and impaired dopamine release. In contrast, inhibition of mTORC2 has more subtle effects, with selective alterations to the output of ventral tegmental area dopamine neurons. Disruption of both mTOR complexes leads to pronounced deficits in dopamine release demonstrating the importance of balanced mTORC1 and mTORC2 signaling for dopaminergic function.

Natal dispersal of large raptors is poorly understood, despite being a crucial transitional life-cycle phase affecting gene flow and population dynamics. A research-gap rarely examined concerns how young dispersing raptors strategize movements towards first settlement on a prospective breeding territory. First territory settlement is a critical decision for a lifetime and can take several years. With such importance, large raptors should theoretically devote considerable effort to acquire accurate information during prospection. Nevertheless, when discovery of territorial opportunities may be difficult, but easier in vacant territories, we posit two extremes in strategizing prospection behaviours: (1) “Quick, grab it when available with limited reconnaissance,” as opposed to (2) “Slow, waiting game with frequent reconnaissance”. We analysed pre-settlement data from 37 GPS-tagged nestling golden eagles, later recorded as having settled on their first territory. The number of eagles’ unique daily visits to their later settled territories was a measure of prospection intensity. We documented substantial variation in prior visits, between less than 10 to several hundred. Analyses considered several potential predictors. We expected a positive association between number of prospecting visits and natal dispersal duration, since with more time to gather information there should be more visits. We also expected fewer prospecting visits in prior vacant territories. Neither of these expectations were supported. There was a non-significant tendency for more prospection visits by males. Our study provides novel information on a seldom-studied behaviour in a large raptor. It illustrates substantial variation in prospecting behaviour, but expectations of potential drivers behind this variation were not confirmed, urging further study.

Migratory birds are birds that fly or move from their breeding place to their non-breeding location. Migratory birds usually migrate to the southern part of the earth or tropical regions to avoid limited resources during winter in their breeding areas (Bildstein, 2006). Bird of Prey or Raptors are a group of birds that frequently migrate. Raptors carry out-migration in several areas which are commonly referred to as flyways. Indonesia is also part of the flight path for migratory birds (Sukmantoro et al., 2007). At this time there were approximately 17 types of migrant raptors in Indonesia. Research on raptor migration has been carried out for a long time in various regions. In the Yogyakarta area, there have been observations of a migrant raptor, but there are no official publications and research on migrant raptor in the Bukit 76 Kaliurang area, Yogyakarta. Therefore this research was conducted to know about migratory raptor in Yogyakarta. This research was conducted at Bukit 76 Kaliurang, Hargobinangun, Pakem, Yogyakarta. The research was conducted in December 2019-March 2020, July-August 2020, and October-November 2020. This research was conductes through observations in the morning at 07.00-11.00 WIB using birdwatching techniques and purposive methods. The results of this study recorded 1 species of migrant raptor, namely the Oriental Honey-buzzard (Pernis ptilorhynchus) and 2 species of resident raptors, namely the Crested Serpent Eagle (Spilornis cheela) and the Brahminy Kite (Haliastur indus).

Abstract Background Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC). Methods The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC. Results The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 μM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene and protein expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression. Conclusions These results suggest that raptor and rictor have important roles in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal the overexpression of raptor and rictor in HPV-related OPSCC.

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There are serious concerns about the ecological degradation caused by modern agriculture and its impact on top-chains predators. But, scientists still disagree on how to assess which are the winners and losers of Anthropocene biodiversity changes.In this field of research, many studies have been carried out on passerine birds but long-term ones, and especially on raptors, are still missing. Our study reports a twelve-year survey on two diurnal common raptors (the Buzzard, Buteo buteo and the Eurasian kestrel, Falco tinnunculus) facing recent land use changes in Western France farmland landscapes. Precise remote sensing data were analyzed each year, allowing us to precisely describe land use changes and stability along this time series.Buzzards showed reduced abundances in intensified landscapes and responded negatively to wood habitat instability while kestrels were more abundant and stable when areas of meadows increased. According to life history traits of these two-raptor species, we may suppose that buzzards, as generalist predators, mainly suffer of nesting site decrease while kestrels suffer of food depletion and namely voles living in meadows.No decreasing or increasing regional or local trends was observed for buzzards during these 12-years confirming that populations seem adjust their numbers to fit to local resources. Inversely, kestrels exhibit significant population collapses at both regional and local scales.If limiting wood habitats fragmentation or disturbance would optimize buzzard densities, drastic management measures improving surfaces and quality of grassland habitats will be necessary to reverse the decline of the Eurasian kestrel, highlighted by this study.

Abstract Background Accurate quantification of infection intensity is essential to estimate infection patterns of avian haemosporidian parasites in order to understand the evolution of host-parasite associations. Traditional microscopy is cost-effective but requires high-quality blood smears and considerable experience, while the widely used semi-quantitative qPCR methods are mostly employed with ideal, laboratory-based golden samples and standard curves, which may limit the comparison of parasitemia from different laboratories. Methods Here we present a digital droplet PCR (ddPCR) protocol for absolute quantification of avian haemosporidians in raptors. Novel primers were designed that target a conserved fragment of a rRNA region of the mitochondrial genome of the parasites. Sensitivity and repeatability were evaluated compared to qPCR and other assays. Results This ddPCR assay enables accurate quantification of haemosporidian parasites belonging to Plasmodium, Haemoproteus and Leucocytozoon with minimum infection quantities of 10−5 (i.e. one parasite copy in 105 host genomes) without the use of standard curves. Quantities assessed by ddPCR were more accurate than qPCR using the same primers through reduction of non-specific amplification in low-intensity samples. The ddPCR technique was more consistent among technical duplicates and reactions, especially when infection intensities were low, and this technique demonstrated equal sensitivity with high correspondence (R 2 = 0.97) compared to the widely used qPCR assay. Both ddPCR and qPCR identified more positive samples than the standard nested PCR protocol for the cytb gene used for barcoding avian haemosporidians. Conclusions We developed a novel ddPCR assay enabling accurate quantification of avian haemosporidians without golden samples or standard curves. This assay can be used as a robust method for investigating infection patterns in different host-parasite assemblages and can facilitate the comparison of results from different laboratories.

Abstract Background The microorganisms populating the gastro-intestinal tract of vertebrates, collectively known as “microbiota”, play an essential role in digestion and are important in regulating the immune response. Whereas the intestinal microbiota in humans and model organisms has been studied for many years, much less is known about the microbiota populating the intestinal tract of wild animals. Results The relatively large number of raptors admitted to the Tufts Wildlife Clinic on the Cummings School of Veterinary Medicine at Tufts University campus provided a unique opportunity to investigate the bacterial microbiota in these birds. Opportunistic collection of fecal samples from raptors of 7 different species in the orders Strigiformes, Accipitriformes, and Falconiformes with different medical histories generated a collection of 46 microbiota samples. Based on 16S amplicon sequencing of fecal DNA, large β-diversity values were observed. Many comparisons exceeded weighted UniFrac distances of 0.9. Microbiota diversity did not segregate with the taxonomy of the host; no significant difference between microbiota from Strigiformes and from Accipitriformes/Falconiformes were observed. In contrast, in a sample of 22 birds admitted for rehabilitation, a significant effect of captivity was found. The change in microbiota profile was driven by an expansion of the proportion of Actinobacteria. Based on a small number of raptors treated with anti-microbials, no significant effect of these treatments on microbiota α-diversity was observed. Conclusions The concept of “meta-organism conservation”, i.e., conservation efforts focused on the host and its intestinal microbiome has recently been proposed. The observed effect of captivity on the fecal microbiota is relevant to understanding the response of wildlife to captivity and optimizing wildlife rehabilitation and conservation efforts.

Abstract Background The balance between protein synthesis and degradation (proteostasis) is a determining factor for muscle size and function. Signalling via the mammalian target of rapamycin complex 1 (mTORC1) regulates proteostasis in skeletal muscle by affecting protein synthesis and autophagosomal protein degradation. Indeed, genetic inactivation of mTORC1 in developing and growing muscle causes atrophy resulting in a lethal myopathy. However, systemic dampening of mTORC1 signalling by its allosteric inhibitor rapamycin is beneficial at the organismal level and increases lifespan. Whether the beneficial effect of rapamycin comes at the expense of muscle mass and function is yet to be established. Methods We conditionally ablated the gene coding for the mTORC1‐essential component raptor in muscle fibres of adult mice [inducible raptor muscle‐specific knockout (iRAmKO)]. We performed detailed phenotypic and biochemical analyses of iRAmKO mice and compared them with muscle‐specific raptor knockout (RAmKO) mice, which lack raptor in developing muscle fibres. We also used polysome profiling and proteomics to assess protein translation and associated signalling in skeletal muscle of iRAmKO mice. Results Analysis at different time points reveal that, as in RAmKO mice, the proportion of oxidative fibres decreases, but slow‐type fibres increase in iRAmKO mice. Nevertheless, no significant decrease in body and muscle mass or muscle fibre area was detected up to 5 months post‐raptor depletion. Similarly, ex vivo muscle force was not significantly reduced in iRAmKO mice. Despite stable muscle size and function, inducible raptor depletion significantly reduced the expression of key components of the translation machinery and overall translation rates. Conclusions Raptor depletion and hence complete inhibition of mTORC1 signalling in fully grown muscle leads to metabolic and morphological changes without inducing muscle atrophy even after 5 months. Together, our data indicate that maintenance of muscle size does not require mTORC1 signalling, suggesting that rapamycin treatment is unlikely to negatively affect muscle mass and function.

Abstract Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)‐URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.

Background & Aims: Intestinal crypts have a remarkable capacity to regenerate after injury from loss of crypt base columnar (CBC) stem cells. After injury, facultative stem cells (FSCs) are activated to replenish the epithelium and replace lost CBCs. Our aim was to assess the role of insulin-like growth factor-1 (IGF-1) to activate FSCs for crypt repair. Methods: The intestinal regenerative response was measured after whole body 12-Gy γ-irradiation of adult mice. IGF-1 signaling or its downstream effector mammalian target of rapamycin complex 1 (mTORC1) was inhibited by administering BMS-754807 or rapamycin, respectively. Mice with inducible Rptor gene deletion were studied to test the role of mTORC1 signaling in the intestinal epithelium. FSC activation post-irradiation was measured by lineage tracing. Results: We observed a coordinate increase in growth factor expression, including IGF-1, at 2 days post-irradiation, followed by a surge in mTORC1 activity during the regenerative phase of crypt repair at day 4. IGF-1 was localized to pericryptal mesenchymal cells, and IGF-1 receptor was broadly expressed in crypt progenitor cells. Inhibition of IGF-1 signaling via BMS-754807 treatment impaired crypt regeneration after 12-Gy irradiation, with no effect on homeostasis. Similarly, rapamycin inhibition of mTORC1 during the growth factor surge blunted the regenerative response. Analysis of Villin-CreERT2;Rptorfl/fl mice showed that epithelial mTORC1 signaling was essential for crypt regeneration. Lineage tracing from Bmi1-marked cells showed that rapamycin blocked FSC activation post-irradiation. Conclusions: Our study shows that IGF-1 signaling through mTORC1 drives crypt regeneration. We propose that IGF-1 release from pericryptal cells stimulates mTORC1 in FSCs to regenerate lost CBCs.

As the demand for carbon-neutral energy sources increases, so does the need to understand the impacts that these technologies have on the environment. Here, we assess the potential consequences of additional mortality on an Endangered raptor recently exposed to wind farms for the first time, the Black Harrier Circus maurus, one of the world’s rarest harriers. We conduct a population viability assessment using a Bayesian model integrating life-history information and annual reporting rates from detection/non-detection surveys from the South African Bird Atlas Project. Our model estimates a global population of approximately 1300 birds currently declining at 2.3% per year, and one that could collapse in under 100 years, if an average of three to five adult birds are killed annually. This level of mortality may soon exist, given the current rate of fatalities and the number of wind farms planned within the species’ distribution. In addition, we find that the population is sensitive to changes in climate. Our results highlight the critical need for appropriate placement, and adaptive management of wind farms and other infrastructure causing harrier mortality. We also show how detection/non-detection data may be used to infer population dynamics and viability, when population counts are unavailable.

Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) were investigated in muscle samples from common kestrels (Falco tinnunculus), eagle owls (Bubo bubo), and little owls (Athene noctua) collected in Beijing, China. The concentrations of PCDD/Fs were in the ranges of 22.7–5280, 67.5–1610, and 68.4–3180 pg/g lipid weight (lw), while levels of dioxin-like PCBs ranged from 4.91 to 1560, 8.08–294, and 28.2–3540 ng/g lw, in common kestrel, eagle owl, and little owl, respectively. The main PCDD/Fs congener was 2,3,4,7,8-PeCDF, and CB-153 dominated the seven indicator PCBs. PCB levels have shown a decreasing trend in the last decade for the common kestrel, but not for little owl in Beijing, which exhibited higher levels of pollutants and toxic equivalency (TEQ) values than the other two species. Concentrations of PCDD/Fs, dioxin-like PCBs, and indicator PCBs differed between fledgling and adult raptors for certain species. Raptors in this study generally had a higher TEQ than the no-observed-effect level in the literature, indicating significant exposure risks to PCDD/Fs and dioxin-like PCBs in raptors, especially in adult little owls.

Energy infrastructure, particularly for wind power, is rapidly expanding in Africa, creating the potential for conflict with at-risk wildlife populations. Raptor populations are especially susceptible to negative impacts of fatalities from wind energy because individuals tend to be long-lived and reproduce slowly. A major determinant of risk of collision between flying birds and wind turbines is the altitude above ground at which a bird flies. We examine 18,710 observations of flying raptors recorded in southern Africa and we evaluate, for 49 species, the frequency with which they were observed to fly at the general height of a wind turbine rotor-swept zone (50–150 m). Threatened species, especially vultures, were more likely to be observed at turbine height than were other species, suggesting that these raptors are most likely to be affected by wind power development across southern Africa. Our results highlight that threatened raptor species, particularly vultures, might be especially impacted by expanded wind energy infrastructure across southern Africa.

The Mountain Hawk-Eagles (Nisaetus nipalensis) is a large raptor native to Asia. Despite the wide distribution of this species, their vocalizations have been described only occasionally, and no studies have provided detailed outcomes for other researchers to follow. This study aimed to obtain systematic and comprehensive results on the vocalizations of the Mountain Hawk-Eagle and a preliminary understanding of its vocal behavior in terms of temporal changes. This study performed a road transect survey along two forestry roads between January 2006 and December 2008 in Taitung County. Two nests were found and observed upstream of the Dazhu and Fangshan streams during the breeding season in 2007 and 2010, respectively. All vocalizations, vocal behavior, and behavior context were recorded. Mountain Hawk-Eagles were discovered to produce at least seven types of vocalization depending on context and structure. The flying call was recorded throughout the year and was made by both sexes. Some vocalizations were recorded only during the breeding season or could only be identified around the nest area; for example, the female begging call, juvenile begging call, and alarm call. From the road transect survey and observation of nests during breeding seasons, we discovered temporal variation in the call rate of the Mountain Hawk-Eagle. The findings and recordings made in this study provide insight into the vocal behavior of the Mountain Hawk-Eagle, but further investigations are needed.

Global climate change has advanced the breeding phenology of many avian species. However, raptors’ breeding phenologies may not respond in the same way to the factors that influence passerine breeding dates. We studied reproduction of suburban and rural Red-shouldered Hawks (Buteo lineatus) in southern Ohio, United States, from 1997 to 2020. Mean hatching dates for 786 broods were 24 April [Julian day: 114.1 ± 0.3 d (SE)] for suburban birds and 25 April (Julian day: 114.5 ± 0.4) for rural birds. Egg-laying date averages approximately 33 days before hatching date, or about the third week of March. We used mixed models to test which factors influenced nestling hatching dates from 1997 to 2020. The best model included year, days of snow cover during the pre-laying period (February–March), and mean March temperature, with days of snow cover having the largest effect. Hatching date (in Julian days) was positively related to snow cover and negatively related to air temperature, i.e., young hatched earlier in years with fewer days of snow cover and in warmer years). Young also hatched slightly later as the study progressed. Overall, neither mean hatching date nor any of the weather variables showed a significant trend over the course of the study. Previously published reports indicate that many raptor species do not exhibit advancing hatching dates, and breeding phenologies often reflect local weather conditions. The complexity and diversity of raptor responses to climate change underscore the importance of long-term studies of raptors at multiple locations.

Abstract Background Birds of prey (raptors) are dominant apex predators in terrestrial communities, with hawks (Accipitriformes) and falcons (Falconiformes) hunting by day and owls (Strigiformes) hunting by night. Results Here, we report new genomes and transcriptomes for 20 species of birds, including 16 species of birds of prey, and high-quality reference genomes for the Eurasian eagle-owl (Bubo bubo), oriental scops owl (Otus sunia), eastern buzzard (Buteo japonicus), and common kestrel (Falco tinnunculus). Our extensive genomic analysis and comparisons with non-raptor genomes identify common molecular signatures that underpin anatomical structure and sensory, muscle, circulatory, and respiratory systems related to a predatory lifestyle. Compared with diurnal birds, owls exhibit striking adaptations to the nocturnal environment, including functional trade-offs in the sensory systems, such as loss of color vision genes and selection for enhancement of nocturnal vision and other sensory systems that are convergent with other nocturnal avian orders. Additionally, we find that a suite of genes associated with vision and circadian rhythm are differentially expressed in blood tissue between nocturnal and diurnal raptors, possibly indicating adaptive expression change during the transition to nocturnality. Conclusions Overall, raptor genomes show genomic signatures associated with the origin and maintenance of several specialized physiological and morphological features essential to be apex predators.