Pathological Bergmann glia alterations and disrupted calcium dynamics in ataxic Canavan disease mice.

Canavan disease (CD) is a recessively inherited pediatric leukodystrophy resulting from inactivating mutations to the oligodendroglial enzyme aspartoacylase (ASPA). ASPA is responsible for hydrolyzing the amino acid derivative N-acetyl-L-aspartate (NAA), and without it, brain NAA concentrations increase by 50% or more. Infants and children with CD present with progressive cognitive and motor delays, cytotoxic edema, astroglial vacuolation, and prominent spongiform brain degeneration. ASPA-deficient CD mice (Aspanur7/nur7 ) present similarly with elevated NAA, widespread astroglial dysfunction, ataxia, and Purkinje cell (PC) dendritic atrophy. Bergmann glia (BG), radial astrocytes essential for cerebellar development, are intimately intertwined with PCs, where they regulate synapse stability, functionality, and plasticity. BG damage is common to many neurodegenerative conditions and frequently associated with PC dysfunction and ataxia. Here, we report that, in CD mice, BG exhibit significant morphological alterations, decreased structural associations with PCs, loss of synaptic support proteins, and altered calcium dynamics. We also find that BG dysfunction predates cerebellar vacuolation and PC damage in CD mice. Previously, we developed an antisense oligonucleotide (ASO) therapy targeting Nat8l (N-acetyltransferase-8-like, "Nat8l ASO") that inhibits the production of NAA and reverses ataxia and PC atrophy in CD mice. Here, we show that Nat8l ASO administration in adult CD mice also leads to BG repair. Furthermore, blocking astroglial uptake of NAA is neuroprotective in astroglia-neuron cocultures exposed to elevated NAA. Our findings suggest that restoration of BG structural and functional integrity could be a mechanism for PC regeneration and improved motor function.

Ablating the Transporter Sodium-Dependent Dicarboxylate Transporter 3 Prevents Leukodystrophy in Canavan Disease Mice.

Canavan disease is caused by ASPA mutations that diminish brain aspartoacylase activity, and it is characterized by excessive brain storage of the aspartoacylase substrate, N-acetyl-l-aspartate (NAA), and by astroglial and intramyelinic vacuolation. Astroglia and the arachnoid mater express sodium-dependent dicarboxylate transporter (NaDC3), encoded by SLC13A3, a sodium-coupled transporter for NAA and other dicarboxylates. Constitutive Slc13a3 deletion in aspartoacylase-deficient Canavan disease mice prevents brain NAA overaccumulation, ataxia, and brain vacuolation. ANN NEUROL 2021;90:845-850.

Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice.

Marked elevation in the brain concentration of N-acetyl-L-aspartate (NAA) is a characteristic feature of Canavan disease, a vacuolar leukodystrophy resulting from deficiency of the oligodendroglial NAA-cleaving enzyme aspartoacylase. We now demonstrate that inhibiting NAA synthesis by intracisternal administration of a locked nucleic acid antisense oligonucleotide to young-adult aspartoacylase-deficient mice reverses their pre-existing ataxia and diminishes cerebellar and thalamic vacuolation and Purkinje cell dendritic atrophy. Ann Neurol 2020;87:480-485.

Strengthening protected areas for biodiversity and ecosystem services in China.

Recent expansion of the scale of human activities poses severe threats to Earth's life-support systems. Increasingly, protected areas (PAs) are expected to serve dual goals: protect biodiversity and secure ecosystem services. We report a nationwide assessment for China, quantifying the provision of threatened species habitat and four key regulating services-water retention, soil retention, sandstorm prevention, and carbon sequestration-in nature reserves (the primary category of PAs in China). We find that China's nature reserves serve moderately well for mammals and birds, but not for other major taxa, nor for these key regulating ecosystem services. China's nature reserves encompass 15.1% of the country's land surface. They capture 17.9% and 16.4% of the entire habitat area for threatened mammals and birds, but only 13.1% for plants, 10.0% for amphibians, and 8.5% for reptiles. Nature reserves encompass only 10.2-12.5% of the source areas for the four key regulating services. They are concentrated in western China, whereas much threatened species' habitat and regulating service source areas occur in eastern provinces. Our analysis illuminates a strategy for greatly strengthening PAs, through creating the first comprehensive national park system of China. This would encompass both nature reserves, in which human activities are highly restricted, and a new category of PAs for ecosystem services, in which human activities not impacting key services are permitted. This could close the gap in a politically feasible way. We also propose a new category of PAs globally, for sustaining the provision of ecosystems services and achieving sustainable development goals.

Mammal recovery inside and outside terrestrial protected areas.

Protected areas are a key component of global conservation, and the world is aiming to increase protected areas to cover 30% of land and water through the 30 × 30 Initiative under the Post-2020 Global Biodiversity Framework. However, factors affecting their success or failure in regard to promoting mammal population recovery are not well studied, particularly using quantitative approaches comparing across diverse taxa, biomes, and countries. To better understand how protected areas contribute to mammalian recovery, we conducted an analysis of 2706 mammal populations both inside and outside of protected areas worldwide. We calculated the annual percent change of mammal populations within and outside of terrestrial protected areas and examined the relationship between the percent change and a suite of human and natural characteristics including biome, region, International Union for Conservation of Nature (IUCN) protected area category, IUCN Red List classification, and taxonomic order. Our results show that overall mammal populations inside and outside of protected areas are relatively stable. It appears that Threatened mammals are doing better inside of protected areas than outside, whereas the opposite is true for species of least concern and Near Threatened species. We also found significant population increases in protected areas classified as category III and significant population decreases in protected and unprotected areas throughout Oceania. Our results demonstrate that terrestrial protected areas can be an important approach for mammalian recovery and conservation.

Heterogeneous and interactive effects of payments for ecosystem services on household income across giant panda nature reserves.

Numerous Payments for Ecosystem Services (PES) programs have been implemented simultaneously around the world but their outcomes in the literature are not consistent and their interactive effects remain understudied. The Natural Forest Conservation Program (NFCP) and Grain to Green Program (GTGP) are two largest PES programs in the world, and many studies have evaluated their effects on household income. However, the identified effects often varied across different studies and the factors explaining this variation are poorly understood. This study used linear regression and geographic detector analysis, based on questionnaire survey data from 14 giant panda natural reserves (NRs) in southwestern China, to evaluate the effects of the NFCP and GTGP on household income and the factors which moderate these effects. The results revealed that the effects of two PES programs on household income were spatially heterogeneous and enhanced by each other and livelihood activities, suggesting a synergistic interaction between policies and livelihood activities, particularly tourism. This study also found that livelihoods activities (e.g., labor migration and tourism), household capital (i.e., house area and farmland area) and demographic factors (i.e., number of labor and non-labor members), exhibit spatial heterogeneity in their effects on household income across NRs. These findings underscore the importance of considering local socioeconomic conditions and the interaction between policy and socio-economic conditions in PES program design to achieve desired outcomes, providing insights for policymakers and practitioners worldwide.

Astroglial conditional Slc13a3 knockout is therapeutic in murine Canavan leukodystrophy.

Canavan disease is a leukodystrophy caused by ASPA mutations that diminish oligodendroglial aspartoacylase activity, and is characterized by markedly elevated brain concentrations of the aspartoacylase substrate N-acetyl-l-aspartate (NAA) and by astroglial and intramyelinic vacuolation. Astroglia express NaDC3 (encoded by SLC13A3), a sodium-coupled transporter for NAA and other dicarboxylates. Astroglial conditional Slc13a3 deletion in aspartoacylase-deficient Canavan disease model mice ("CD mice") reversed brain NAA elevation and improved motor function. These results demonstrate that astroglial NaDC3 contributes to brain NAA elevation in CD mice, and suggest that suppressing astroglial NaDC3 activity would ameliorate human Canavan disease.

Characterizing the metabolome and microbiome at giant panda scent marking sites during the mating season.

Scent marking sites served as a primary means of chemical communication for giant pandas, enabling intraspecific communication. We integrated metabolomics and high-throughput sequencing techniques to examine the non-targeted metabolome and microbial community structure of scent marking sites and feces in the field. Integrative analysis revealed a more comprehensive array of chemical compounds compared to previous investigations, including ketones, acids, heterocycles, alcohols, and aldehydes. Notably, specific compounds such as 2-decenal, (E)-, octanal, decanal, L-α-terpineol, vanillin, and nonanal emerged as potential key players in scent signaling. Intriguingly, our study of the microbial domain identified dominant bacterial species from the Actinobacteria, Bacteroidetes, and Proteobacteria phyla, likely orchestrating metabolic processes at scent marking sites. Comparative analyses showed, for the first time, that feces do not share the same functions as scent markers, indicating distinct functional roles. This research deepens scientific understanding of chemical communication in wild pandas.

Effects of climate warming on soil nitrogen cycles and bamboo growth in core giant panda habitat.

Climate change can pose a significant threat to terrestrial ecosystems by disrupting the circulation of soil nitrogen. However, experimental analyses on the effect of climate change on soil nitrogen cycles and the implications for the conservation of key wildlife species (i.e., the giant panda, Ailuropoda melanoleuca) remain understudied. We investigated the effects of a 1.5 °C, 3 °C, and 4.5 °C temperature increase on nitrogen distribution in different soil layers of bamboo forest via an in-situ experiment and assessed the implications for the growth and survival of arrow bamboo (Bashania faberi), a critical food resource for giant pandas. Our results showed that warming treatments generally increased soil N content, while effects differed between surface soil and subsurface soil and at different warming treatments. Particularly an increase of 1.5 °C raised the subsurface soil NO3-N content, as well as the content of N in bamboo leaves. We found a significant positive correlation between the subsurface soil NO3-N content and the N content of arrow bamboo. An increase of 3-4.5 °C raised the content of total N and NO3-N in the surface soil and led to a reduction in the total aboveground biomass and survival rate of arrow bamboo. Limited warming (e.g., the increase of 0-1.5 °C) may promote the soil N cycle, raise the N-acetylglucosaminidase (NAG) enzyme activity, increase NO3-N in subsurface soil, increase the N content of bamboo, and boost the biomass of bamboo - all of which could be beneficial to giant panda survival. However, higher warming (e.g., an increase of 3-4.5 °C) resulted in mass death of bamboo and a large reduction in aboveground biomass. Our findings provide a cautiously optimistic scenario for bamboo forest ecosystems under low levels of warming over a short period of time, but risks from higher levels of warming may be serious, especially considering the unpredictability of global climatic change.

Implications of human-wildlife conflict on the diet of an endangered avian top predator in the northern Andes.

Conflicts between rural people and the Endangered Black-and-chestnut Eagle (Spizaetus isidori) are a prominent conservation concern in the northern Andes, as at least 60 eagles were poached between 2000 and 2022 in response to poultry predation. Here, we conducted direct observations to analyze the Black-and-chestnut Eagle diet and evaluated how forest cover affects the feeding habits of the species during nestling-rearing periods in 16 nests located in different human-transformed Andean landscapes of Ecuador and Colombia. We analyzed 853 prey items (46 species) delivered to nestlings. We used Generalized Linear Models to test whether the percent forest cover calculated within varying buffer distances around each nest and linear distances from the nest to the nearest settlement and pasture areas were predictors of diet diversity and biomass contribution of prey. Forest cover was not a factor that affected the consumption of poultry; however, the eagle regularly preyed on chickens (Gallus gallus) (i.e., domestic Galliformes) which were consumed by 15 of the 16 eagle pairs, with biomass contributions (14.57% ± 10.55) representing 0.6-37% of the total prey consumed. The Black-and-chestnut Eagle is an adaptable generalist able to switch from mammalian carnivores to guans (i.e., wild Galliformes) in human-dominated landscapes, and eagles nesting in sites with low forest cover had a less diverse diet than those in areas with more intact forests. Management actions for the conservation of this avian top predator require studies on the eagle's diet in areas where human persecution is suspected or documented, but also maintaining forest cover for the wild prey of the species, development of socio-economic and psychological assessments on the drivers behind human-eagle conflicts, and the strengthening of technical capacities of rural communities, such as appropriate poultry management.

How perceived exposure to environmental harm influences environmental behavior in urban China.

Rapid environmental degradation in China makes understanding how perceived exposure to environmental harm influences environmental attitudes and participation in pro-environmental behaviors among the Chinese people crucial. We used a nation-wide survey dataset in urban China to test two hypotheses: experiencing environmental harm directly affects environmental behavior; environmental attitudes mediate the relationship between experiencing environmental harm and environmental behavior. We found respondents who experienced environmental harm had more pro-environmental attitudes. Experiencing environmental harm positively influenced pro-environmental behavior both directly and indirectly through the mediation of pro-environmental attitudes. Among the pro-environmental behaviors, environmental litigation was most strongly related with exposure to environmental harm. Our results suggest that more participation in pro-environmental behaviors may be expected as rapid economic development increases public exposure to environmental harm in urban China.

A Coupled Human and Natural Systems Framework to Characterize Emerging Infectious Diseases-The Case of Fibropapillomatosis in Marine Turtles.

Emerging infectious diseases of wildlife have markedly increased in the last few decades. Unsustainable, continuous, and rapid alterations within and between coupled human and natural systems have significantly disrupted wildlife disease dynamics. Direct and indirect anthropogenic effects, such as climate change, pollution, encroachment, urbanization, travel, and trade, can promote outbreaks of infectious diseases in wildlife. We constructed a coupled human and natural systems framework identifying three main wildlife disease risk factors behind these anthropogenic effects: (i) immune suppression, (ii) viral spillover, and (iii) disease propagation. Through complex and convoluted dynamics, each of the anthropogenic effects and activities listed in our framework can lead, to some extent, to one or more of the identified risk factors accelerating disease outbreaks in wildlife. In this review, we present a novel framework to study anthropogenic effects within coupled human and natural systems that facilitate the emergence of infectious disease involving wildlife. We demonstrate the utility of the framework by applying it to Fibropapillomatosis disease of marine turtles. We aim to articulate the intricate and complex nature of anthropogenically exacerbated wildlife infectious diseases as multifactorial. This paper supports the adoption of a One Health approach and invites the integration of multiple disciplines for the achievement of effective and long-lasting conservation and the mitigation of wildlife emerging diseases.

Spatial density estimate of the snow leopard, Panthera uncia, in the Central Tibetan Plateau, China.

Knowledge of large carnivore population abundance is essential for wildlife management and conservation, but these data are often difficult to obtain in inherently low-density species. In particular, the snow leopard, Panthera uncia, an enigmatic cat occupying remote mountains in Central Asia, has received insufficient assessments of its population abundance because of logistical and methodological challenges. Here, we aimed to develop a robust density estimation of snow leopards based on 81 days of camera trapping within a contiguous and previously unsurveyed 1950 km2 area of habitat on the Tibetan Plateau (Mayue Township, Shenzha County, Tibet Autonomous Region, China). By applying spatially explicit capture-recapture models, we produced an estimate of 1.40 (95%CI: 1.06-1.84) individuals per 100 km2 . Results also suggested sex-specific variation in the range of movement around activity centers, with male (N = 10, σ = 4.02) movement considerably greater than female (N = 8, σ = 1.84) movement. The findings can serve as a reliable baseline reference for assessing the population trends of this endangered felid species with future estimates. This study will provide context to contribute toward a better understanding of ecological factors shaping the distribution and abundance of snow leopards and the related conservation measures needed to sustain their long-term survival on the Tibetan Plateau.

Relationship of the estrogen surge and multiple mates to cub paternity in the giant panda (Ailuropoda melanoleuca): implications for optimal timing of copulation or artificial insemination.

The effectiveness of ex situ breeding programs for endangered species can be limited by challenges in mimicking mating competitions that naturally occur among multiple mates in the wild. The objective of this study was to evaluate the impact of timed natural matings and/or artificial inseminations in the context of the urinary estrogen surge on cub production in the giant panda (Ailuropoda melanoleuca). We used a large cohort of giant pandas, including 12 females and 17 males. DNA paternity exclusion was used to pinpoint accurately the interval during the estrogen surge that coincided with the ideal sperm deposition time to produce offspring. Of the 31 cubs (in 19 pregnancies), 22 (71.0%; 15 pregnancies) were produced from matings occurring on the day of or the day after the maximal urinary estrogen peak. Sixteen of the 19 pregnancies (84.2%) produced at least one offspring sired by the first male mating with the dam. There was a preponderance of twins (12 of 19; 63.2%), and dual paternities were discovered in 3 of 12 twin sets (25%). These findings indicate a strong relationship between the excreted estrogen surge and sperm deposition to achieve pregnancy in the giant panda. To ensure the production of the most genetically diverse young, it is imperative that the most appropriate male mate first and on the day of or the day after the highest detected estrogen value. There is no advantage to increasing the number of copulations or mating partners within 1 day of the estrogen peak on the incidence of twinning, although this practice may increase the prevalence of dual paternity in cases of multiple births.

Factors affecting the outcome of artificial insemination using cryopreserved spermatozoa in the giant panda (Ailuropoda melanoleuca).

Artificial insemination (AI) is an important component of captive breeding programs for endangered species, such as the giant panda. The panda has been the subject of increasingly successful captive breeding programs involving a compilation of assisted breeding techniques, including AI using cryopreserved spermatozoa. AI implementation is currently hampered by a lack of understanding of the factors that may cause failure. We investigated factors influencing the probability of success of AI for 14 giant panda females housed at the China Center for Research and Conservation of the Giant Panda (CCRCGP) inseminated in a total of 20 instances using cryopreserved spermatozoa from 11 males currently residing in 6 different captive breeding institutions. One of the pandas was the oldest giant panda female to ever successfully conceive from AI (20.5 years old). The success of AI was significantly affected by the timing of AI in relationship to both timing of peak urinary estrogen of the female and percent decline in urinary estrogen between the peak level and the first AI attempt. Our results suggest that the window for successful AI in giant pandas may be narrower than previously suspected, although individual differences in rates of decline in urinary estrogen may reflect some degree of variation in this crucial window across females. Our results are consistent with recent research on pandas and other species that demonstrates the efficacy of cryopreserved spermatozoa for AI and highlights the need for more in-depth analysis of factors related to female physiology that may influence its success.

The Influence of Environmental Variables on Home Range Size and Use in the Golden Snub-Nosed Monkey (Rhinopithecus roxellana) in Tangjiahe National Nature Reserve, China.

Accurate descriptions of home ranges can provide important information for understanding animal ecology and behavior and contribute to the formulation of conservation strategies. We used the grid cell method and kernel density estimation (KDE) to estimate the home range size of golden snub-nosed monkeys (Rhinopithecus roxellana) in Tangjiahe National Nature Reserve. We also used Moran's eigenvector maps analysis and variation partitioning to test the influence of environmental variables on home range use. The seasonal home range size was 15.4 km2 in spring, 11.6 km2 in summer, 13.7 km2 in autumn, and 15.6 km2 in winter, based on the grid cell method. The seasonal core area of 50% KDE was 9.86 km2 in spring, 5.58 km2 in summer, 7.20 km2 in autumn, and 4.23 km2 in winter. The environmental variables explained 63.60% of home range use intensity in spring, 72.21% in summer, 26.52% in autumn, and none in winter, and some environmental variables contributed to the spatial variation in home range use intensity. Water sources, tree density, and dominant trees of Chinese wingnut (Pterocarya stenoptera) were the important environmental factors determining home range use. These environmental factors require protection to ensure the survival of the golden snub-nosed monkey.

SOX2 is essential for astrocyte maturation and its deletion leads to hyperactive behavior in mice.

Children with SOX2 deficiency develop ocular disorders and extra-ocular CNS anomalies. Animal data show that SOX2 is essential for retinal and neural stem cell development. In the CNS parenchyma, SOX2 is primarily expressed in astroglial and oligodendroglial cells. Here, we report a crucial role of astroglial SOX2 in postnatal brain development. Astroglial Sox2-deficient mice develop hyperactivity in locomotion and increased neuronal excitability in the corticostriatal circuit. Sox2 deficiency inhibits postnatal astrocyte maturation molecularly, morphologically, and electrophysiologically without affecting astroglia proliferation. Mechanistically, SOX2 directly binds to a cohort of astrocytic signature and functional genes, the expression of which is significantly reduced in Sox2-deficient CNS and astrocytes. Consistently, Sox2 deficiency remarkably reduces glutamate transporter expression and compromised astrocyte function of glutamate uptake. Our study provides insights into the cellular mechanisms underlying brain defects in children with SOX2 mutations and suggests a link of astrocyte SOX2 with extra-ocular abnormalities in SOX2-mutant subjects.