FOXO1 couples metabolic activity and growth state in the vascular endothelium.

Endothelial cells (ECs) are plastic cells that can switch between growth states with different bioenergetic and biosynthetic requirements. Although quiescent in most healthy tissues, ECs divide and migrate rapidly upon proangiogenic stimulation. Adjusting endothelial metabolism to the growth state is central to normal vessel growth and function, yet it is poorly understood at the molecular level. Here we report that the forkhead box O (FOXO) transcription factor FOXO1 is an essential regulator of vascular growth that couples metabolic and proliferative activities in ECs. Endothelial-restricted deletion of FOXO1 in mice induces a profound increase in EC proliferation that interferes with coordinated sprouting, thereby causing hyperplasia and vessel enlargement. Conversely, forced expression of FOXO1 restricts vascular expansion and leads to vessel thinning and hypobranching. We find that FOXO1 acts as a gatekeeper of endothelial quiescence, which decelerates metabolic activity by reducing glycolysis and mitochondrial respiration. Mechanistically, FOXO1 suppresses signalling by MYC (also known as c-MYC), a powerful driver of anabolic metabolism and growth. MYC ablation impairs glycolysis, mitochondrial function and proliferation of ECs while its EC-specific overexpression fuels these processes. Moreover, restoration of MYC signalling in FOXO1-overexpressing endothelium normalizes metabolic activity and branching behaviour. Our findings identify FOXO1 as a critical rheostat of vascular expansion and define the FOXO1-MYC transcriptional network as a novel metabolic checkpoint during endothelial growth and proliferation.

Age at first reproduction in wolves: different patterns of density dependence for females and males.

Age at first reproduction constitutes a key life-history trait in animals and is evolutionarily shaped by fitness benefits and costs of delayed versus early reproduction. The understanding of how intrinsic and extrinsic changes affects age at first reproduction is crucial for conservation and management of threatened species because of its demographic effects on population growth and generation time. For a period of 40 years in the Scandinavian wolf (Canis lupus) population, including the recolonization phase, we estimated age at first successful reproduction (pup survival to at least three weeks of age) and examined how the variation among individuals was explained by sex, population size (from 1 to 74 packs), primiparous or multiparous origin, reproductive experience of the partner and inbreeding. Median age at first reproduction was 3 years for females (n = 60) and 2 years for males (n = 74), and ranged between 1 and 8-10 years of age (n = 297). Female age at first reproduction decreased with increasing population size, and increased with higher levels of inbreeding. The probability for males to reproduce later first decreased, reaching its minimum when the number of territories approached 40-60, and then increased with increasing population size. Inbreeding for males and reproductive experience of parents and partners for both sexes had overall weak effects on age at first reproduction. These results allow for more accurate parameter estimates when modelling population dynamics for management and conservation of small and vulnerable wolf populations, and show how humans through legal harvest and illegal hunting influence an important life-history trait like age at first reproduction.

Scavenging in the Anthropocene: Human impact drives vertebrate scavenger species richness at a global scale.

Understanding the distribution of biodiversity across the Earth is one of the most challenging questions in biology. Much research has been directed at explaining the species latitudinal pattern showing that communities are richer in tropical areas; however, despite decades of research, a general consensus has not yet emerged. In addition, global biodiversity patterns are being rapidly altered by human activities. Here, we aim to describe large-scale patterns of species richness and diversity in terrestrial vertebrate scavenger (carrion-consuming) assemblages, which provide key ecosystem functions and services. We used a worldwide dataset comprising 43 sites, where vertebrate scavenger assemblages were identified using 2,485 carcasses monitored between 1991 and 2018. First, we evaluated how scavenger richness (number of species) and diversity (Shannon diversity index) varied among seasons (cold vs. warm, wet vs. dry). Then, we studied the potential effects of human impact and a set of macroecological variables related to climatic conditions on the scavenger assemblages. Vertebrate scavenger richness ranged from species-poor to species rich assemblages (4-30 species). Both scavenger richness and diversity also showed some seasonal variation. However, in general, climatic variables did not drive latitudinal patterns, as scavenger richness and diversity were not affected by temperature or rainfall. Rainfall seasonality slightly increased the number of species in the community, but its effect was weak. Instead, the human impact index included in our study was the main predictor of scavenger richness. Scavenger assemblages in highly human-impacted areas sustained the smallest number of scavenger species, suggesting human activity may be overriding other macroecological processes in shaping scavenger communities. Our results highlight the effect of human impact at a global scale. As species-rich assemblages tend to be more functional, we warn about possible reductions in ecosystem functions and the services provided by scavengers in human-dominated landscapes in the Anthropocene.

Guanine nucleotide-binding proteins of the G12 family shape immune functions by controlling CD4+ T cell adhesiveness and motility.

Integrin-mediated adhesion plays a central role in T cell trafficking and activation. Genetic inactivation of the guanine nucleotide-binding (G) protein alpha-subunits Galpha(12) and Galpha(13) resulted in an increased activity of integrin leukocyte-function-antigen-1 in murine CD4(+) T cells. The interaction with allogeneic dendritic cells was enhanced, leading to an abnormal proliferative response in vitro. In vivo, T cell-specific inactivation of Galpha(12) and Galpha(13) caused lymphadenopathy due to increased lymph node entry and enhanced T cell proliferation, and the susceptibility toward T cell-mediated diseases was enhanced. Mechanistically, we show that in the absence of Galpha(12) and Galpha(13) the activity of the small GTPases Rac1 and Rap1 was increased, whereas signaling of the small GTPase RhoA was strongly reduced. Our data indicate that locally produced mediators signal through Galpha(12)- and Galpha(13)-coupled receptors to negatively regulate cell polarization and adhesiveness, thereby fine-tuning T cell trafficking, proliferation, and susceptibility toward T cell-mediated diseases.

Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase.

Notch signalling is a key intercellular communication mechanism that is essential for cell specification and tissue patterning, and which coordinates critical steps of blood vessel growth. Although subtle alterations in Notch activity suffice to elicit profound differences in endothelial behaviour and blood vessel formation, little is known about the regulation and adaptation of endothelial Notch responses. Here we report that the NAD(+)-dependent deacetylase SIRT1 acts as an intrinsic negative modulator of Notch signalling in endothelial cells. We show that acetylation of the Notch1 intracellular domain (NICD) on conserved lysines controls the amplitude and duration of Notch responses by altering NICD protein turnover. SIRT1 associates with NICD and functions as a NICD deacetylase, which opposes the acetylation-induced NICD stabilization. Consequently, endothelial cells lacking SIRT1 activity are sensitized to Notch signalling, resulting in impaired growth, sprout elongation and enhanced Notch target gene expression in response to DLL4 stimulation, thereby promoting a non-sprouting, stalk-cell-like phenotype. In vivo, inactivation of Sirt1 in zebrafish and mice causes reduced vascular branching and density as a consequence of enhanced Notch signalling. Our findings identify reversible acetylation of the NICD as a molecular mechanism to adapt the dynamics of Notch signalling, and indicate that SIRT1 acts as rheostat to fine-tune endothelial Notch responses.

Pyrimidine Pathway-Dependent and -Independent Functions of the Toxoplasma gondii Mitochondrial Dihydroorotate Dehydrogenase.

Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of de novo pyrimidine biosynthesis and is a proven drug target for inducing immunosuppression in therapy of human disease as well as a rapidly emerging drug target for treatment of malaria. In Toxoplasma gondii, disruption of the first, fifth, or sixth step of de novo pyrimidine biosynthesis induced uracil auxotrophy. However, previous attempts to generate uracil auxotrophy by genetically deleting the mitochondrion-associated DHODH of T. gondii (TgDHODH) failed. To further address the essentiality of TgDHODH, mutant gene alleles deficient in TgDHODH activity were designed to ablate the enzyme activity. Replacement of the endogenous DHODH gene with catalytically deficient DHODH gene alleles induced uracil auxotrophy. Catalytically deficient TgDHODH localized to the mitochondria, and parasites retained mitochondrial membrane potential. These results show that TgDHODH is essential for the synthesis of pyrimidines and suggest that TgDHODH is required for a second essential function independent of its role in pyrimidine biosynthesis.

Leave before it's too late: anthropogenic and environmental triggers of autumn migration in a hunted ungulate population.

Autumn has to a large extent been neglected in the climate effect literature, yet autumn events, e.g., plant senescence and animal migration, affect fitness of animals differently than spring events. Understanding how variables including plant phenology influence timing of autumn migrations is important to gain a comprehensive understanding of the full annual cycle of migratory species. Here we use 13 yr of data from 60 male and 168 female red deer (Cervus elaphus) to identify triggers of autumn migration. We relate the timing of autumn migration to environmental variables like snow fall, temperature, and plant phenology (NDVI), and to onset of hunting, sex, and migration distance. Severe weather has been suggested as the main trigger of autumn migration, but we found that the majority of the individuals had left the summer range well before snow fall (80.3%) and frost (70.5%), and also before the peak deterioration in forage quality (71.9%). Declining temperatures were associated with a higher daily migration potential. Onset of hunting showed the largest effect on migration potential, with a marked increase during the first days of hunting. Individuals still present in the summer range when snow fall, frost, or peak forage deterioration occurred showed a significantly higher migration potential around these events. Males were less responsive to environmental cues, suggesting rutting activity, starting earlier in males, initiate movement prior to such conditions. Also, individuals with longer migration distances had a higher migration potential late in the season than individuals with shorter migration distances. Our study shows that factors beyond weather and plant phenology, such as onset of hunting, may be important triggers of autumn migration. Severe weather and forage deterioration were important triggers for the individuals experiencing this, which suggests a hierarchical response to environmental cues. The trade-off between staying longer in the summer range and increased energy expenditures if surprised by severe weather is asymmetric, and leaving well in advance can be seen as a risk-averse tactic.

Leave before it's too late: anthropogenic and environmental triggers of autumn migration in a hunted ungulate population.

Autumn has to a large extent been neglected in the climate effect literature, yet autumn events, e.g., plant senescence and animal migration, affect fitness of animals differently than spring events. Understanding how variables including plant phenology influence timing of autumn migrations is important to gain a comprehensive understanding of the full annual cycle of migratory species. Here we use 13 yr of data from 60 male and 168 female red deer (Cervus elaphus) to identify triggers of autumn migration. We relate the timing of autumn migration to environmental variables like snow fall, temperature, and plant phenology (NDVI), and to onset of hunting, sex, and migration distance. Severe weather has been suggested as the main trigger of autumn migration, but we found that the majority of the individuals had left the summer range well before snow fall (80.3%) and frost (70.5%), and also before the peak deterioration in forage quality (71.9%). Declining temperatures were associated with a higher daily migration potential. Onset of hunting showed the largest effect on migration potential, with a marked increase during the first days of hunting. Individuals still present in the summer range when snow fall, frost, or peak forage deterioration occurred showed a significantly higher migration potential around these events. Males were less responsive to environmental cues, suggesting rutting activity, starting earlier in males, initiate movement prior to such conditions. Also, individuals with longer migration distances had a higher migration potential late in the season than individuals with shorter migration distances. Our study shows that factors beyond weather and plant phenology, such as onset of hunting, may be important triggers of autumn migration. Severe weather and forage deterioration were important triggers for the individuals experiencing this, which suggests a hierarchical response to environmental cues. The trade-off between staying longer in the summer range and increased energy expenditures if surprised by severe weather is asymmetric, and leaving well in advance can be seen as a risk-averse tactic.

Sarcoptic mange in the Scandinavian wolf Canis lupus population.

BACKGROUND: Sarcoptic mange, a parasitic disease caused by the mite Sarcoptes scabiei, is regularly reported on wolves Canis lupus in Scandinavia. We describe the distribution and transmission of this parasite within the small but recovering wolf population by analysing 269 necropsy reports and performing a serological survey on 198 serum samples collected from free-ranging wolves between 1998 and 2013. RESULTS: The serological survey among 145 individual captured Scandinavian wolves (53 recaptures) shows a consistent presence of antibodies against sarcoptic mange. Seropositivity among all captured wolves was 10.1 % (CI. 6.4 %-15.1 %). Sarcoptic mange-related mortality reported at necropsy was 5.6 % and due to secondary causes, predominantly starvation. In the southern range of the population, seroprevalence was higher, consistent with higher red fox densities. Female wolves had a lower probability of being seropositive than males, but for both sexes the probability increased with pack size. Recaptured individuals changing from seropositive to seronegative suggest recovery from sarcoptic mange. The lack of seropositive pups (8-10 months, N = 56) and the occurrence of seropositive and seronegative individuals in the same pack indicates interspecific transmission of S. scabiei into this wolf population. CONCLUSIONS: We consider sarcoptic mange to have little effect on the recovery of the Scandinavian wolf population. Heterogenic infection patterns on the pack level in combination with the importance of individual-based factors (sex, pack size) and the north-south gradient for seroprevalence suggests low probability of wolf-to-wolf transmission of S. scabiei in Scandinavia.

Predator-dependent functional response in wolves: from food limitation to surplus killing.

The functional response of a predator describes the change in per capita kill rate to changes in prey density. This response can be influenced by predator densities, giving a predator-dependent functional response. In social carnivores which defend a territory, kill rates also depend on the individual energetic requirements of group members and their contribution to the kill rate. This study aims to provide empirical data for the functional response of wolves Canis lupus to the highly managed moose Alces alces population in Scandinavia. We explored prey and predator dependence, and how the functional response relates to the energetic requirements of wolf packs. Winter kill rates of GPS-collared wolves and densities of cervids were estimated for a total of 22 study periods in 15 wolf territories. The adult wolves were identified as the individuals responsible for providing kills to the wolf pack, while pups could be described as inept hunters. The predator-dependent, asymptotic functional response models (i.e. Hassell-Varley type II and Crowley-Martin) performed best among a set of 23 competing linear, asymptotic and sigmoid models. Small wolf packs acquired >3 times as much moose biomass as required to sustain their field metabolic rate (FMR), even at relatively low moose abundances. Large packs (6-9 wolves) acquired less biomass than required in territories with low moose abundance. We suggest the surplus killing by small packs is a result of an optimal foraging strategy to consume only the most nutritious parts of easy accessible prey while avoiding the risk of being detected by humans. Food limitation may have a stabilizing effect on pack size in wolves, as supported by the observed negative relationship between body weight of pups and pack size.

Decomposing risk: landscape structure and wolf behavior generate different predation patterns in two sympatric ungulates.

Recolonizing carnivores can have a large impact on the status of wild ungulates, which have often modified their behavior in the absence of predation. Therefore, understanding the dynamics of reestablished predator-prey systems is crucial to predict their potential ecosystem effects. We decomposed the spatial structure of predation by recolonizing wolves (Canis lupus) on two sympatric ungulates, moose (Alces alces) and roe deer (Capreolus capreolus), in Scandinavia during a 10-year study. We monitored 18 wolves with GPS collars, distributed over 12 territories, and collected records from predation events. By using conditional logistic regression, we assessed the contributions of three main factors, the utilization patterns of each wolf territory, the spatial distribution of both prey species, and fine-scale landscape structure, in determining the spatial structure of moose and roe deer predation risk. The reestablished predator-prey system showed a remarkable spatial variation in kill occurrence at the intra-territorial level, with kill probabilities varying by several orders of magnitude inside the same territory. Variation in predation risk was evident also when a spatially homogeneous probability for a wolf to encounter a prey was simulated. Even inside the same territory, with the same landscape structure, and when exposed to predation by the same wolves, the two prey species experienced an opposite spatial distribution of predation risk. In particular, increased predation risk for moose was associated with open areas, especially clearcuts and young forest stands, whereas risk was lowered for roe deer in the same habitat types. Thus, fine-scale landscape structure can generate contrasting predation risk patterns in sympatric ungulates, so that they can experience large differences in the spatial distribution of risk and refuge areas when exposed to predation by a recolonizing predator. Territories with an earlier recolonization were not associated with a lower hunting success for wolves. Such constant efficiency in wolf predation during the recolonization process is in line with previous findings about the naive nature of Scandinavian moose to wolf predation. This, together with the human-dominated nature of the Scandinavian ecosystem, seems to limit the possibility for wolves to have large ecosystem effects and to establish a behaviorally mediated trophic cascade in Scandinavia.

Scavenging patterns of an inbred wolf population in a landscape with a pulse of human-provided carrion.

Scavenging is an important part of food acquisition for many carnivore species that switch between scavenging and predation. In landscapes with anthropogenic impact, humans provide food that scavenging species can utilize. We quantified the magnitude of killing versus scavenging by gray wolves (Canis lupus) in Scandinavia where humans impact the ecosystem through hunter harvest, land use practices, and infrastructure. We investigated the cause of death of different animals utilized by wolves, and examined how the proportion of their consumption time spent scavenging was influenced by season, wolf social affiliation, level of inbreeding, density of moose (Alces alces) as their main prey, density of brown bear (Ursus arctos) as an intraguild competitor, and human density. We used data from 39 GPS-collared wolves covering 3198 study days (2001-2019), including 14,205 feeding locations within space-time clusters, and 1362 carcasses utilized by wolves. Most carcasses were wolf-killed (80.5%) while a small part had died from other natural causes (1.9%). The remaining had either anthropogenic mortality causes (4.7%), or the cause of death was unknown (12.9%). Time spent scavenging was higher during winter than during summer and autumn. Solitary wolves spent more time scavenging than pack-living individuals, likely because individual hunting success is lower than pack success. Scavenging time increased with the mean inbreeding coefficient of the adult wolves, possibly indicating that more inbred individuals resort to scavenging, which requires less body strength. There was weak evidence for competition between wolves and brown bears as well as a positive relationship between human density and time spent scavenging. This study shows how both intrinsic and extrinsic factors drive wolf scavenging behavior, and that despite a high level of inbreeding and access to carrion of anthropogenic origin, wolves mainly utilized their own kills.

New Insights into rice pyrimidine catabolic enzymes.

Introduction: Rice is a primary global food source, and its production is affected by abiotic stress, caused by climate change and other factors. Recently, the pyrimidine reductive catabolic pathway, catalyzed by dihydropyrimidine dehydrogenase (DHPD), dihydropyrimidinase (DHP) and ß-ureidopropionase (ß-UP), has emerged as a potential participant in the abiotic stress response of rice. Methods: The rice enzymes were produced as recombinant proteins, and two were kinetically characterized. Rice dihydroorotate dehydrogenase (DHODH), an enzyme of pyrimidine biosynthesis often confused with DHPD, was also characterized. Salt-sensitive and salt-resistant rice seedlings were subjected to salt stress (24 h) and metabolites in leaves were determined by mass spectrometry. Results: The OsDHPD sequence was homologous to the C-terminal half of mammalian DHPD, conserving FMN and uracil binding sites, but lacked sites for Fe/S clusters, FAD, and NADPH. OsDHPD, truncated to eliminate the chloroplast targeting peptide, was soluble, but inactive. Database searches for polypeptides homologous to the N-terminal half of mammalian DHPD, that could act as co-reductants, were unsuccessful. OsDHODH exhibited kinetic parameters similar to those of other plant DHODHs. OsDHP, truncated to remove a signal sequence, exhibited a kcat/Km = 3.6 x 103 s-1M-1. Osb-UP exhibited a kcat/Km = 1.8 x 104 s-1M-1. Short-term salt exposure caused insignificant differences in the levels of the ureide intermediates dihydrouracil and ureidopropionate in leaves of salt-sensitive and salt-resistant plants. Allantoin, a ureide metabolite of purine catabolism, was found to be significantly higher in the resistant cultivar compared to one of the sensitive cultivars. Discussion: OsDHP, the first plant enzyme to be characterized, showed low kinetic efficiency, but its activity may have been affected by truncation. Osb-UP exhibited kinetic parameters in the range of enzymes of secondary metabolism. Levels of two pathway metabolites were similar in sensitive and resistant cultivars and appeared to be unaffected by short-term salt exposure."

Small rodent monitoring at Birkebeiner Road, Norway.

Background: Northern small mammal populations are renowned for their multi-annual population cycles. Population cycles are multi-faceted and have extensive impacts on the rest of the ecosystem. In 2011, we started a student-based research activity to monitor the variation of small rodent density along an elevation gradient following the Birkebeiner Road, in southeast Norway. Fieldwork was conducted by staff and students at the University campus Evenstad, Inland Norway University of Applied Sciences, which has a long history of researching cyclic population dynamics. The faculty has a strong focus on engaging students in all parts of the research activities, including data collection. Small rodents were monitored using a set of snap trap stations. Trapped animals were measured (e.g. body mass, body length, sex) and dissected to assess their reproductive status. We also characterised the vegetation at trapping sites. New information: We provide a dataset of small rodent observations that show fluctuating population dynamics across an elevation gradient (300 m to 1,100 m a.s.l) and in contrasting habitats. This dataset encompasses three peaks of the typical 3-4-year vole population cycles; the number of small rodents and shrews captured show synchrony and peaked in years 2014, 2017 and 2021. The bank vole Myodesglareolus was by far (87%) the most common species trapped, but also other species were observed (including shrews). We provide digital data collection forms and highlight the importance of long-term data collection.

Hepatic hematopoiesis in the alpaca (Vicugna pacos), a species with development in hypoxic environments.

Hematopoiesis occurs in different anatomical niches throughout the life of the individual. The first hematopoietic extra-embryonic stage is replaced by a intra-embryonic stage that occurs in a region that is adjacent to the dorsal aorta. Then, the prenatal hematopoietic function is continued by the liver and spleen, and later by the bone marrow. The objective of the present work was to describe the morphological characteristics of hepatic hematopoiesis in the alpaca and to analyze the proportion of the hematopoietic compartment of the organ and the cell types, at different times of ontogeny. Sixty-two alpaca samples were collected from the municipal slaughterhouse of Huancavelica, Perú. They were processed by routine histological techniques. Hematoxylin-eosin staining, special dyes, immunohistochemical techniques and supplementary analyses by lectinhistochemistry, were performed. The prenatal liver is an important structure in the expansion and differentiation of hematopoietic stem cells. Their hematopoietic activity was characterized by four stages: initiation, expansion, peak, and involution. The liver started its hematopoietic function at 21 days EGA and it was maintained until shortly before birth. Differences were found in the proportion and morphology of the hematopoietic tissue in the different groups corresponding to each gestational stage.

A migratory northern ungulate in the pursuit of spring: jumping or surfing the green wave?

The forage-maturation hypothesis (FMH) states that herbivores migrate along a phenological gradient of plant development in order to maximize energy intake. Despite strong support for the FMH, the actual relationship between plant phenology and ungulate movement has remained enigmatic. We linked plant phenology (MODIS-normalized difference vegetation index [NDVI] data) and space use of 167 migratory and 78 resident red deer (Cervus elaphus), using a space-time-time matrix of "springness," defined as the instantaneous rate of green-up. Consistent with the FMH, migrants experienced substantially greater access to early plant phenology than did residents. Deer were also more likely to migrate in areas where migration led to greater gains in springness. Rather than "surfing the green wave" during migration, migratory red deer moved rapidly from the winter to the summer range, thereby "jumping the green wave." However, migrants and, to a lesser degree, residents did track phenological green-up through parts of the growing season by making smaller-scale adjustments in habitat use. Despite pronounced differences in their life histories, we found only marginal differences between male and female red deer in this study. Those differences that we did detect pointed toward additional constraints on female space-use tactics, such as those posed by calving and caring for dependent offspring. We conclude that whereas in some systems migration itself is a way to surf the green wave, in others it may simply be a means to reconnect with phenological spring at the summer range. In the light of ubiquitous anthropogenic environmental change, understanding the relationship between the green wave and ungulate space use has important consequences for the management and conservation of migratory ungulates and the phenomenon of migration itself.

Predicting the potential demographic impact of predators on their prey: a comparative analysis of two carnivore-ungulate systems in Scandinavia.

1. Understanding the role of predation in shaping the dynamics of animal communities is a fundamental issue in ecological research. Nevertheless, the complex nature of predator-prey interactions often prevents researchers from modelling them explicitly. 2. By using periodic Leslie-Usher matrices and a simulation approach together with parameters obtained from long-term field projects, we reconstructed the underlying mechanisms of predator-prey demographic interactions and compared the dynamics of the roe deer-red fox-Eurasian lynx-human harvest system with those of the moose-brown bear-gray wolf-human harvest system in the boreal forest ecosystem of the southern Scandinavian Peninsula. 3. The functional relationship of both roe deer and moose λ to changes in predation rates from the four predators was remarkably different. Lynx had the strongest impact among the four predators, whereas predation rates by wolves, red foxes, or brown bears generated minor variations in prey population λ. Elasticity values of lynx, wolf, fox and bear predation rates were -0·157, -0·056, -0·031 and -0·006, respectively, but varied with both predator and prey densities. 4. Differences in predation impact were only partially related to differences in kill or predation rates, but were rather a result of different distribution of predation events among prey age classes. Therefore, the age composition of killed individuals emerged as the main underlying factor determining the overall per capita impact of predation. 5. Our results confirm the complex nature of predator-prey interactions in large terrestrial mammals, by showing that different carnivores preying on the same prey species can exert a dramatically different demographic impact, even in the same ecological context, as a direct consequence of their predation patterns. Similar applications of this analytical framework in other geographical and ecological contexts are needed, but a more general evaluation of the subject is also required, aimed to assess, on a broader systematic and ecological range, what specific traits of a carnivore are most related to its potential impact on prey species.

The importance of evaluating standard monitoring methods: Observer bias and detection probabilities for moose pellet group surveys.

Counting is not always a simple exercise. Specimens can be misidentified or not detected when they are present, giving rise to unidentified sources of error. Deer pellet group counts are a common method to monitor abundance, density, and population trend. Yet, detection errors and observer bias could introduce error into sometimes very large (spatially, temporally) datasets. For example, in Scandinavia, moose (Alces alces) pellet group counts are conducted by volunteer hunters and students, but it is unknown how much uncertainty observer error introduces into these datasets. Our objectives were to 1) estimate the detection probability of moose pellet groups; 2) identify the primary variables leading to detection errors including prior observer experience; and 3) compare density estimates using single and double observer counts. We selected a subset of single observer plots from a long-term monitoring project to be conducted as dependent double observer surveys, where primary and secondary observers worked simultaneously in the field. We did this to quantify detection errors for moose pellet groups, which were previously unknown in Scandinavia, and to identify covariates which introduced variation into our estimates. Our study area was in the boreal forests of southern Norway where we had a nested grid of 100-m2 plots that we surveyed each spring. Our observers were primarily inexperienced. We found that when pellet groups were detected by the primary observer, the secondary observer saw additional pellet groups 42% of the time. We found search time was the primary covariate influencing detection. We also found density estimates from double observer counts were 1.4 times higher than single observer counts, for the same plots. This density underestimation from single observer surveys could have consequences to managers, who sometimes use pellet counts to set harvest quotas. We recommend specific steps to improve future moose pellet counts.

Rewilding by Wolf Recolonisation, Consequences for Ungulate Populations and Game Hunting.

The ongoing recolonisations of human-transformed environments in Europe by large carnivores like the wolf Canis lupus means that conservation conflicts could re-surface, among other reasons, due to predation on ungulate game species. We estimated the effect of wolves on ungulate species using data on wolf prey selection, kill rates and territory size to build a hypothetical case of future expansion. We extrapolated results on predation from the current wolf distribution in central Sweden and eastern Poland to the eventual wolf recolonisation of southern Sweden. We then calculated the proportion of five ungulate game species killed annually by wolves, and the ratio between the predicted annual predation by wolves given future colonization and the number of ungulates currently harvested by hunters. Results showed that wolf recolonization in southern Sweden would have a minor impact on the estimated population densities of red deer Cervus elaphus, fallow deer Dama dama and wild boar Sus scrofa, but is likely to lead to a significant reduction in human captures of moose Alces alces and roe deer Capreolus capreolus. The current five-ungulate species system in southern Sweden suggests a potential for two to four times higher wolf density than the two-ungulate species system in the northern part of their current distribution. Management and conservation of recolonizing large carnivores require a better understanding of the observed impact on game populations under similar ecological conditions to ameliorate conservation conflicts and achieve a paradigm of coexistence. Integrating these predictions into management is paramount to the current rewilding trend occurring in many areas of Europe or North America.

A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth.

Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue's metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are instructed by Yes-associated protein 1 (YAP)/WW domain-containing transcription regulator 1 (WWTR1/TAZ)-transcriptional enhanced associate domain (TEAD): a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP/TAZ or their transcriptional partners, TEAD1, 2 and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP/TAZ promote angiogenesis by fuelling nutrient-dependent mTORC1 signalling. By orchestrating the transcription of a repertoire of cell-surface transporters, including the large neutral amino acid transporter SLC7A5, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 activation. Dissociating mTORC1 from these nutrient inputs-elicited by the loss of Rag GTPases-inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. Together, these findings define a pivotal role for YAP/TAZ-TEAD in controlling endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.