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While agricultural intensification and expansion are major factors driving loss and degradation of natural habitat and species decline, some wildlife species also benefit from agriculturally managed habitats. This may lead to high population densities with impacts on both human livelihoods and wildlife conservation. Cranes are a group of 15 species worldwide, affected both negatively and positively by agricultural practices. While eleven species face critical population declines, numbers of common cranes (Grus grus) and sandhill cranes (Grus canadensis) have increased drastically in the last 40 years. Their increase is associated with higher incidences of crane foraging on agricultural crops, causing financial losses to farmers. Our aim was to synthesize scientific knowledge on the bilateral effects of land use change and crane populations. We conducted a systematic literature review of peer‐reviewed publications on agriculture‐crane interactions (n = 135) and on the importance of agricultural crops in the diet of cranes (n = 81). Agricultural crops constitute a considerable part of the diet of all crane species (average of 37%, most frequently maize (Zea mays L.) and wheat (Triticum aestivum L.)). Crop damage was identified in only 10% of all agriculture‐crane interactions, although one‐third of interactions included cranes foraging on cropland. Using a conceptual framework analysis, we identified two major pathways in agriculture‐crane interactions: (1) habitat loss with negative effects on crane species dependent on specific habitats, and (2) expanding agricultural habitats with superabundant food availability beneficial for opportunistic crane species. The degree to which crane species can adapt to agricultural land use changes may be an important factor explaining their population response. We conclude that multi‐objective management needs to combine land sparing and land sharing strategies at landscape scale. To support viable crane populations while guaranteeing sustainable agricultural production, it is necessary to include the perspectives of diverse stakeholders and streamline conservation initiatives and agricultural policy accordingly.  相似文献   

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BackgroundAortic regurgitation is the most common cardiovascular damage in Chinese patients with Behçet’s disease (BD) and is usually associated with aortic disease. These patients are easily misdiagnosed, and their prognosis is poor, even after surgical treatment. This study aimed to analyse potential factors that can improve the prognosis of BD patients with aortic regurgitation and/or aortic involvement.MethodsTwenty-two patients with diagnosed or suspected BD as well as aortic regurgitation and/or aortic involvement in our hospital from 2012 through 2017 were collected in this study. Their clinical characteristics were listed, and the diagnosis of BD was evaluated by two different criteria sets. The influences of surgical treatment and immunosuppressive therapy (IST) on their prognosis were also explored.ResultsThe diagnostic positive rate of the International Criteria for Behçet’s Disease was higher than that of the International Study Group criteria (kappa value 0.31, p < 0.05), indicating that the diagnostic consistency between the criteria sets was poor. There was no significant difference in survival between patients who had undergone ≤ 1 operation and those with ≥ 2 operations. Aortic valve replacement alone or in combination with aortic root replacement had no significant effect on the incidence of reoperation or death, but IST did significantly reduce this incidence (p < 0.05). However, there was no significant difference in the occurrence of reoperation or death between preoperative and postoperative IST versus postoperative IST only.ConclusionIST significantly improved the prognosis of BD patients with aortic regurgitation and/or aortic involvement.Supplementary InformationThe online version of this article (10.1007/s12471-021-01567-6) contains supplementary material, which is available to authorized users.  相似文献   

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  1. Both climate change and human exploitation are major threats to plant life in mountain environments. One species that may be particularly sensitive to both of these stressors is the iconic alpine flower edelweiss (Leontopodium alpinum Colm.). Its populations have declined across Europe due to over‐collection for its highly prized flowers. Edelweiss is still subject to harvesting across the Romanian Carpathians, but no study has measured to what extent populations are vulnerable to anthropogenic change.
  2. Here, we estimated the effects of climate and human disturbance on the fitness of edelweiss. We combined demographic measurements with predictions of future range distribution under climate change to assess the viability of populations across Romania.
  3. We found that per capita and per‐area seed number and seed mass were similarly promoted by both favorable environmental conditions, represented by rugged landscapes with relatively cold winters and wet summers, and reduced exposure to harvesting, represented by the distance of plants from hiking trails. Modeling these responses under future climate scenarios suggested a slight increase in per‐area fitness. However, we found plant ranges contracted by between 14% and 35% by 2050, with plants pushed into high elevation sites.
  4. Synthesis. Both total seed number and seed mass are expected to decline across Romania despite individual edelweiss fitness benefiting from a warmer and wetter climate. More generally, our approach of coupling species distribution models with demographic measurements may better inform conservation strategies of ways to protect alpine life in a changing world.
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5.
Background: Behçet’s disease (BD) is a rare chronic multisystemic vasculitis of unknown etiology. It is usually diagnosed between the 2nd and 4th decades of life, so its association with pregnancy is not unusual. This study aims to characterize the evolution of pregnancy in a group of pregnant women with BD and the impact of this pathology in embryo-fetal morbidity. Methods: A retrospective case-control study included 49 pregnancies in women suffering from BD, followed in our institution. Pregnancy outcomes were compared with a control group of healthy pregnant women. Two controls per case were randomly selected. Statistical analysis used SPSS 25.0, and a p-value of 0.05 was considered statistically significant. Results: Forty-nine pregnancies were included in 27 patients with BD. BD exacerbation occurred in 32.6% of the pregnancies. There were no significant statistical differences between the two groups regarding the rate of preterm delivery, gestational diabetes, and preeclampsia (p>0.05). In the BD group, we found a higher rate of miscarriage (24.5%) and fetal growth restriction (FGR, 13.3%, p<0.05). In the study group, 13 (32.5%) of the pregnant patients did not need treatment. The cesarean rate was significantly higher in the BD group (43.2% vs 20.4% in the control group, p<0.05), and there were no significant differences in median gestational age at the time of delivery (p>0.05). The birth weight of newborns did not differ significantly between the groups. There was no association of BD with maternal morbidity and neonatal complications. Conclusion: In this study, the majority of pregnant with BD did not present clinical exacerbation of their pathology. However, BD may have an adverse influence on pregnancy outcomes. FGR and miscarriage rates were significantly higher in the study group.  相似文献   

6.
As a result of extensive data collection efforts over the last 20–30 years, there is quite a good understanding of the large‐scale geographic distribution and range limits of African great apes. However, as human activities increasingly fragment great ape spatial distribution, a better understanding of what constitutes suitable great ape habitat is needed to inform conservation and resource extraction management. Chimpanzees (Pan troglodytes troglodytes) and gorillas (Gorilla gorilla gorilla) inhabit the Lobéké National Park and its surrounding forest management units (FMUs) in South‐East Cameroon. Both park and neighboring forestry concessions require reliable evidence on key factors driving great ape distribution for their management plans, yet this information is largely missing and incomplete. This study aimed at mapping great ape habitat suitability in the area and at identifying the most influential predictors among three predictor categories, including landscape predictors (dense forest, swampy forest, distance to water bodies, and topography), human disturbance predictors (hunting, deforestation, distance to roads, and population density), and bioclimatic predictor (annual precipitation). We found that about 63% of highly to moderately suitable chimpanzee habitat occurred within the Lobéké National Park, while only 8.4% of similar habitat conditions occurred within FMUs. For gorillas, highly and moderately suitable habitats occurred within the Lobéké National Park and its surrounding FMUs (82.6% and 65.5%, respectively). Key determinants of suitable chimpanzee habitat were hunting pressure and dense forest, with species occurrence probability optimal at relatively lower hunting rates and at relatively high‐dense forest areas. Key determinants of suitable gorilla habitat were hunting pressure, dense forests, swampy forests, and slope, with species occurrence probability optimal at relatively high‐dense and swampy forest areas and at areas with mild slopes. Our findings show differential response of the two ape species to forestry activities in the study area, thus aligning with previous studies.  相似文献   

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Urbanization is expanding worldwide with major consequences for organisms. Anthropogenic factors can reduce the fitness of animals but may have benefits, such as consistent human food availability. Understanding anthropogenic trade‐offs is critical in environments with variable levels of natural food availability, such as the Galápagos Islands, an area of rapid urbanization. For example, during dry years, the reproductive success of bird species, such as Darwin''s finches, is low because reduced precipitation impacts food availability. Urban areas provide supplemental human food to finches, which could improve their reproductive success during years with low natural food availability. However, urban finches might face trade‐offs, such as the incorporation of anthropogenic debris (e.g., string, plastic) into their nests, which may increase mortality. In our study, we determined the effect of urbanization on the nesting success of small ground finches (Geospiza fuliginosa; a species of Darwin''s finch) during a dry year on San Cristóbal Island. We quantified nest building, egg laying and hatching, and fledging in an urban and nonurban area and characterized the anthropogenic debris in nests. We also documented mortalities including nest trash‐related deaths and whether anthropogenic materials directly led to entanglement‐ or ingestion‐related nest mortalities. Overall, urban finches built more nests, laid more eggs, and produced more fledglings than nonurban finches. However, every nest in the urban area contained anthropogenic material, which resulted in 18% nestling mortality while nonurban nests had no anthropogenic debris. Our study showed that urban living has trade‐offs: urban birds have overall higher nesting success during a dry year than nonurban birds, but urban birds can suffer mortality from anthropogenic‐related nest‐materials. These results suggest that despite potential costs, finches benefit overall from urban living and urbanization may buffer the effects of limited resource availability in the Galápagos Islands.  相似文献   

9.
The jaguarundi (Puma yagouaroundi) is a small felid with a historical range from central Argentina through southern Texas. Information on the current distribution of this reclusive species is needed to inform recovery strategies in the United States where its last record was in 1986 in Texas. From 2003 to 2021, we conducted camera‐trap surveys across southern Texas and northern Tamaulipas, México to survey for medium‐sized wild cats (i.e., ocelots [Leopardus pardalis], bobcats [Lynx rufus], and jaguarundi). After 350,366 trap nights at 685 camera sites, we did not detect jaguarundis at 16 properties or along 2 highways (1050 km2) in Texas. However, we recorded 126 jaguarundi photographic detections in 15,784 trap nights on 2 properties (125.3 km2) in the northern Sierra of Tamaulipas, Tamaulipas, México. On these properties, latency to detection was 72 trap nights, with a 0.05 probability of detection per day and 0.73 photographic event rate every 100 trap nights. Due to a lack of confirmed class I sightings (e.g., specimen, photograph) in the 18 years of this study, and no other class I observations since 1986 in the United States, we conclude that the jaguarundi is likely extirpated from the United States. Based on survey effort and results from México, we would have expected to detect jaguarundis over the course of the study if still extant in Texas. We recommend that state and federal agencies consider jaguarundis as extirpated from the United States and initiate recovery actions as mandated in the federal jaguarundi recovery plan. These recovery actions include identification of suitable habitat in Texas, identification of robust populations in México, and re‐introduction of the jaguarundi to Texas.  相似文献   

10.
  1. The estimation of abundance and distribution and factors governing patterns in these parameters is central to the field of ecology. The continued development of hierarchical models that best utilize available information to inform these processes is a key goal of quantitative ecologists. However, much remains to be learned about simultaneously modeling true abundance, presence, and trajectories of ecological communities.
  2. Simultaneous modeling of the population dynamics of multiple species provides an interesting mechanism to examine patterns in community processes and, as we emphasize herein, to improve species‐specific estimates by leveraging detection information among species. Here, we demonstrate a simple but effective approach to share information about observation parameters among species in hierarchical community abundance and occupancy models, where we use shared random effects among species to account for spatiotemporal heterogeneity in detection probability.
  3. We demonstrate the efficacy of our modeling approach using simulated abundance data, where we recover well our simulated parameters using N‐mixture models. Our approach substantially increases precision in estimates of abundance compared with models that do not share detection information among species. We then expand this model and apply it to repeated detection/non‐detection data collected on six species of tits (Paridae) breeding at 119 1 km2 sampling sites across a Pmontanus hybrid zone in northern Switzerland (2004–2020). We find strong impacts of forest cover and elevation on population persistence and colonization in all species. We also demonstrate evidence for interspecific competition on population persistence and colonization probabilities, where the presence of marsh tits reduces population persistence and colonization probability of sympatric willow tits, potentially decreasing gene flow among willow tit subspecies.
  4. While conceptually simple, our results have important implications for the future modeling of population abundance, colonization, persistence, and trajectories in community frameworks. We suggest potential extensions of our modeling in this paper and discuss how leveraging data from multiple species can improve model performance and sharpen ecological inference.
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11.
  1. Four events of Placobdella costata sucking human blood are described.
  2. Human blood was sucked by both adult and juvenile specimens of P. costata.
  3. The feeding strategies of juveniles under parental care are presented.
  4. New data on juvenile specimens'' body form are presented.
  5. Information on the potential role of mammals in dispersion and habitat preferences of leeches P. costata is considered.
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12.
The effects of psychotherapies for depression have been examined in several hundreds of randomized trials, but no recent network meta‐analysis (NMA) has integrated the results of these studies. We conducted an NMA of trials comparing cognitive behavioural, interpersonal, psychodynamic, problem‐solving, behavioural activation, life‐review and “third wave” therapies and non‐directive supportive counseling with each other and with care‐as‐usual, waiting list and pill placebo control conditions. Response (50% reduction in symptoms) was the primary outcome, but we also assessed remission, standardized mean difference, and acceptability (all‐cause dropout rate). Random‐effects pairwise and network meta‐analyses were conducted on 331 randomized trials with 34,285 patients. All therapies were more efficacious than care‐as‐usual and waiting list control conditions, and all therapies – except non‐directive supportive counseling and psychodynamic therapy – were more efficacious than pill placebo. Standardized mean differences compared with care‐as‐usual ranged from –0.81 for life‐review therapy to –0.32 for non‐directive supportive counseling. Individual psychotherapies did not differ significantly from each other, with the only exception of non‐directive supportive counseling, which was less efficacious than all other therapies. The results were similar when only studies with low risk of bias were included. Most therapies still had significant effects at 12‐month follow‐up compared to care‐as‐usual, and problem‐solving therapy was found to have a somewhat higher long‐term efficacy than some other therapies. No consistent differences in acceptability were found. Our conclusion is that the most important types of psychotherapy are efficacious and acceptable in the acute treatment of adult depression, with few significant differences between them. Patient preference and availability of each treatment type may play a larger role in the choice between types of psychotherapy, although it is possible that a more detailed characterization of patients with a diagnosis of depression may lead to a more precise matching between individual patients and individual psychotherapies.  相似文献   

13.
Studying the dietary flexibility of primates that live in human‐modified environments is crucial for understanding their ecological adaptations as well as developing management and conservation plans. Southern gelada (Theropithecus gelada obscurus) is an endemic little‐known subspecies of gelada that inhabits human‐modified landscapes in the northern central highlands of Ethiopia. During an 18‐month period, we conducted this intensive study in an unprotected area of a human‐modified landscape at Kosheme in Wollo to investigate the feeding ecology of southern geladas and their dietary responses to seasonal variations. We quantified the monthly and seasonal diet data from a band of southern geladas using instantaneous scan sampling method at 15‐min intervals, and green grass phenology and availability using visual inspection from the randomly selected permanent plots. The overall average diet of southern geladas at Kosheme constituted grass blades 55.4%, grass undergrounds 13.2%, grass bulbs 5.6%, grass seeds 5.4%, herb leaves 4.0, fruits 7.3%, and cereal crops 5.6%. Grass blade consumption increased with increasing green grass availability, while underground food consumption increased with decreasing green grass availability, and vice versa. Southern geladas spent significantly more time feeding on the grass blades and herb leaves and significantly less time on bulbs during the wet season than the dry season. Underground grass items (rhizomes and corms) were not consumed during the wet season, but made up 22.3% of the dry season diet. Thus, although grass blades are staple diet items for geladas, underground diet items are important “fallback foods” at Kosheme. Our result shows insights into the dietary flexibility southern geladas adopt to cope with human‐modified landscapes of the north‐central Ethiopian Highlands. Thus, the study contributes to a better understanding of how changing environments shape primate ecology and evolution.  相似文献   

14.
The aim of this study was to evaluate the effects of adding different concentrations of edible bird’s nest (EBN) which is secreted by swiftlet birds (Aerodramus fuciphagus), into EquiPlus® and E-Z Mixin® extenders on the quality of chilled Arabian stallion semen at various storage times (0, 24 and 48 h). Ten ejaculates were collected from five stallions, and diluted using the two extenders containing 0% (control), 0.12%, 0.24% and 0.24% of EBN + seminal plasma (SP). All the diluted semen samples were then cooled and stored at 5 °C, and examined at 0, 24 and 48 h. Sperm kinetic parameters were assessed using computer assisted sperm analysis (CASA) and viability were assessed using Hoechst33342/PI stain. In both extenders, total motility (TM) and progressive motility (PM) were significantly higher at 0.12% and 0.24% compared to 0.24% + SP at 24 and 48 h. At 0.12%, E-Z mixin® treated semen had significantly higher TM and PM than EquiPlus® at 24 and 48 h. At 0.12% and 0.24%, average path velocity (VAP), straight-line velocity (VSL) and curvilinear velocity (VCL) were significantly higher in E-Z mixin® treated semen compared to EquiPlus® at 24 and 48 h. Comparisons between the two extender types at different concentrations of EBN showed no significant difference in lateral head amplitude (ALH), linearity (LIN), straightness (STR), beat cross frequency (BCF) and viability, irrespective of the storage time. The percentage of viable was significantly higher in E-Z mixin® than EquiPlus® at 0 and 48 h in control and 0.12%. Supplementation of the E-Z mixin® extender with 0.12% and 0.24% EBN concentrations in the absence of SP provided better CASA parameters such as TM, PM, VAP, VSL, and VCL at 24 and 48 h storage time. In conclusion, the results of this study indicated that chilled semen from Arabian stallion that was extended using E-Z mixin® and supplemented with 0.12% and 0.24% EBN concentrations performed better and yielded superior results in sperm kinetic parameters and % viable compared to EquiPlus® at 24 and 48 h storage time.  相似文献   

15.
Brown bear‐mediated conflicts have caused immense economic loss to the local people living across the distribution range. In India, limited knowledge is available on the Himalayan brown bear (HBB), making human–brown bear conflict (HBC) mitigation more challenging. In this study, we studied HBC in the Lahaul valley using a semi‐structured questionnaire survey by interviewing 398 respondents from 37 villages. About 64.8% of respondents reported conflict in two major groups—crop damage (30.6%) and livestock depredations (6.2%), while 28% reported both. Conflict incidences were relatively high in summer and frequently occurred in areas closer to the forest (<500 m) and between the elevations range of 2700 m to 3000 m above sea level (asl). The dependency of locals on forest resources (70%) for their livelihood makes them vulnerable to HBC. The “upper lower” class respondents were most impacted among the various socioeconomic classes. Two of the four clusters were identified as HBC hot spots in Lahaul valley using SaTscan analysis. We also obtained high HBC in cluster II with a 14.35 km radius. We found that anthropogenic food provisioning for HBB, livestock grazing in bear habitats, and poor knowledge of animal behavior among the communities were the major causes of HBC. We suggest horticulture crop waste management, controlled and supervised grazing, ecotourism, the constitution of community watch groups, and others to mitigate HBC. We also recommend notifying a few HBB abundant sites in the valley as protected areas for the long‐term viability of the HBB in the landscape.  相似文献   

16.
Alzheimer''s disease (AD) is an age‐related neurodegenerative disease, and the imbalance between production and clearance of β‐amyloid (Aβ) is involved in its pathogenesis. Autophagy is an intracellular degradation pathway whereby leads to removal of aggregated proteins, up‐regulation of which may be a plausible therapeutic strategy for the treatment of AD. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. Our previous study showed that thioperamide, as an antagonist of H3R, enhances autophagy and protects against ischemic injury. However, the effect of thioperamide on autophagic function and Aβ pathology in AD remains unknown. In this study, we found that thioperamide promoted cognitive function, ameliorated neuronal loss, and Aβ pathology in APP/PS1 transgenic (Tg) mice. Interestingly, thioperamide up‐regulated autophagic level and lysosomal function both in APP/PS1 Tg mice and in primary neurons under Aβ‐induced injury. The neuroprotection by thioperamide against AD was reversed by 3‐MA, inhibitor of autophagy, and siRNA of Atg7, key autophagic‐related gene. Furthermore, inhibition of activity of CREB, H3R downstream signaling, by H89 reversed the effect of thioperamide on promoted cell viability, activated autophagic flux, and increased autophagic‐lysosomal proteins expression, including Atg7, TFEB, and LAMP1, suggesting a CREB‐dependent autophagic activation by thioperamide in AD. Taken together, these results suggested that H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB‐mediated autophagy and lysosomal pathway, which contributed to Aβ clearance. This study uncovered a novel mechanism involving autophagic regulating behind the therapeutic effect of thioperamide in AD.  相似文献   

17.
The competitive relationship and coexistence pattern among close related species have long been one of the hot issues in ecological research. Interspecies interactions can exert important influences on the local distribution of rare species. Black muntjac Muntiacus crinifrons is an endemic species to eastern China, currently restricted to limited regions. In contrast, Chinese muntjac Muntiacus reevesi is the most common and widespread deer in southern China. Both species co‐occur in southern Anhui and western Zhejiang Province. Little is known about the interaction of these two sympatric‐related species. In this study, to investigate the site use determinants and co‐occurrence pattern of the two sympatric muntjac species, we conducted a camera trap survey across about 250 km2 in mountainous area of southern Anhui Province, China. We adopted a multistep approach to incorporate habitat preferences while modeling occupancy and detection. We found that the two species did not separate along elevation gradient (range from 400 m to 1,400 m) as described in previous studies. Results of single‐species occupancy models indicated that elevation had positive effects on the site use of both species, while slope had an opposite influence on their site use. Positive effects of elevation on the site use implied that both species try to avoid human interference at low elevations. Significant negative effect of slope on the site use of black muntjac suggested that the species prefer habitat with gentle slope and avoided steep. Co‐occurrence models and species interaction factors provided evidence that the two muntjac species had an independent occupancy (ψ BM CM = ψ BM cm, SIF = 1) and exhibited a positive species interaction in detection probability (p BM < r BM CM). Combined with the results of previous studies, we suggested that it was fine differentiation in microhabitats and food resources utilization rather spatial or temporal segregation that allowed the two species co‐occurrence. The site use determinants revealed in our study would be useful for the habitat conservation and restoration for the rare black muntjac, and the co‐occurrence pattern of the two sympatric muntjac species could provide useful information for deep understanding of the coexistence mechanism among forest‐dwelling ungulates.  相似文献   

18.
Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) is a pathogenic coronavirus causing COVID‐19 infection. The interaction between the SARS‐CoV‐2 spike protein and the human receptor angiotensin‐converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide‐thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID‐19. However, the molecular‐level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID‐19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID‐19 infection or reducing the severity of the disease.  相似文献   

19.
Aim Understanding which human or environmental factors interact to enable or to limit the occurrence and persistence of large carnivores in human‐dominated landscapes is an important issue for their effective conservation, especially under the current scenario of global change where most of their former habitat is being transformed by humans. Location NW Iberian Peninsula. Methods We combine data on the distribution of Iberian wolves (Canis lupus signatus) living in a human‐dominated landscape in NW Spain and variation and partitioning methods to investigate the relative importance of three groups of predictors: food availability, humans and landscape attributes – each group expected to have unequal effects on wolf reproduction and survival – and their interactions on the occurrence of this species. Results We found that the group of predictors related with landscape attributes (altitude, roughness and refuge) strongly determined wolf occurrence, followed by humans and food availability. Variance partitioning analysis revealed that the three most important components determining wolf occurrence were related with landscape attributes: (1) the joint effects of the three predictor groups, (2) the joint effect of humans and landscape attributes and (3) the pure effect of landscape attributes. Altitude had the main independent contribution to explain the probability of wolf occurrence. Main conclusions In human‐dominated landscapes, the occurrence of wolves is the result of a complex interaction among several environmental and human factors. Our results suggest that the characteristics of the landscape (spatial context) – factors associated with the security of wolves facilitating that animals go unnoticed by humans, wolf movements, dispersal events and short‐time colonization – become more important in human‐dominated landscapes and may have played a key role in the occurrence and persistence of this species throughout decades modulating the relationship between humans and wolf distribution.  相似文献   

20.
The cell‐to‐cell transfer of α‐synuclein (α‐Syn) greatly contributes to Parkinson''s disease (PD) pathogenesis and underlies the spread of α‐Syn pathology. During this process, extracellular α‐Syn can activate microglia and neuroinflammation, which plays an important role in PD. However, the effect of extracellular α‐Syn on microglia autophagy is poorly understood. In the present study, we reported that extracellular α‐Syn inhibited the autophagy initiation, as indicated by LC3‐II reduction and p62 protein elevation in BV2 and cultured primary microglia. The in vitro findings were verified in microglia‐enriched population isolated from αSyn‐overexpressing mice induced by adeno‐associated virus (AAV2/9)‐encoded wildtype human αSyn injection into the substantia nigra (SN). Mechanistically, α‐Syn led to microglial autophagic impairment through activating toll‐like receptor 4 (Tlr4) and its downstream p38 and Akt‐mTOR signaling because Tlr4 knockout and inhibition of p38, Akt as well as mTOR prevented α‐Syn‐induced autophagy inhibition. Moreover, inhibition of Akt reversed the mTOR activation but failed to affect p38 phosphorylation triggered by α‐Syn. Functionally, the in vivo evidence showed that lysozyme 2 Cre (Lyz2 cre)‐mediated depletion of autophagyrelated gene 5 (Atg5) in microglia aggravated the neuroinflammation and dopaminergic neuron losses in the SN and exacerbated the locomotor deficit in αSyn‐overexpressing mice. Taken together, the results suggest that extracellular α‐Syn, via Tlr4‐dependent p38 and Akt‐mTOR signaling cascades, disrupts microglial autophagy activity which synergistically contributes to neuroinflammation and PD development.  相似文献   

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