Relationship Between Climate Change and Marmot Plague of Marmota himalayana Plague Focus - the Altun Mountains of the Qinghai-Xizang Plateau, China, 2000-2022.

Introduction: Plague is a zoonotic disease that occurs naturally in specific geographic areas. Climate change can influence the populations of the plague host or vector, leading to variations in the occurrence and epidemiology of plague in animals. Methods: In this study, we collected meteorological and plague epidemiological data from the Marmota himalayana plague focus in the Altun Mountains of the Qinghai-Xizang Plateau. The data spanned from 2000 to 2022. We describe the climatic factors and plague epidemic conditions and we describe their analysis by Pearson's correlation. Results: During the period from 2000 to 2022, the isolation rates of Yersinia pestis (Y.pestis) from marmots and fleas were 9.27% (451/4,864) and 7.17% (118/1,646), respectively. Additionally, we observed a positive rate of F1 antibody of 11.25% (443/3,937) in marmots and 18.16% (142/782) in dogs. With regards to climate, there was little variation, and a decreasing trend in blowing-sand days was observed. The temperature in the previous year showed a negative correlation with the Y. pestis isolation rate in marmots (r=-0.555, P=0.011) and the positive rate of F1 antibody in marmots (r=-0.552, P=0.012) in the current year. The average annual precipitation in the previous two years showed a positive correlation with marmot density (r=0.514, P=0.024), while blowing-sand days showed a negative correlation with marmot density (r=-0.701, P=0.001). Furthermore, the average annual precipitation in the previous three years showed a positive correlation with the isolation rate of Y. pestis from marmots (r=0.666, P=0.003), and blowing-sand days showed a negative correlation with marmot density (r=-0.597, P=0.009). Conclusions: The findings of this study indicate that there is a hysteresis effect of climate change on the prevalence of plague. Therefore, monitoring climate conditions can offer significant insights for implementing timely preventive and control measures to combat plague epidemics.

Pasteurella multocida strains of a novel capsular serotype and lethal to Marmota himalayana on Qinghai-Tibet plateau in China.

Pasteurella multocida is a zoonotic pathogen causing serious diseases in humans and animals. Here, we report P. multocida from wildlife on China's Qinghai-Tibet plateau with a novel capsular serotype, forming a single branch on the core-genome phylogenetic tree: four strains isolated from dead Himalayan marmot (Marmota himalayana) and one genome assembled from metagenomic sequencing of a dead Woolly hare (Lepus oiostolus). Four of the strains were identified as subspecies multocida and one was septica. The mouse model showed that the challenge strain killed mice within 24 h at an infectious dose of less than 300 bacteria. The short disease course is comparable to septicemic plague: the host has died before more severe pathological changes could take place. Though pathological changes were relatively mild, cytokine storm was obvious with a significant rise of IL-12p70, IL-6, TNF-αand IL-10 (P < 0.05). Our findings suggested P. multocida is a lethal pathogen for wildlife on Qinghai-Tibet plateau, in addition to Yersinia pestis. Individuals residing within the M. himalayana plague focus are at risk for P. multocida infection, and public health warnings are necessitated.

Soil properties and fungal community jointly explain N2O emissions following N and P enrichment in an alpine meadow.

Nutrient enrichment, such as nitrogen (N) and phosphorus (P), typically affects nitrous oxide (N2O) emissions in terrestrial ecosystems, predominantly via microbial nitrification and denitrification processes in the soil. However, the specific impact of soil property and microbial community alterations under N and P enrichment on grassland N2O emissions remains unclear. To address this, a field experiment was conducted in an alpine meadow of the northeastern Qinghai-Tibetan Plateau. This study aimed to unravel the mechanisms underlying N and P enrichment effects on N2O emissions by monitoring N2O fluxes, along with analyzing associated microbial communities and soil physicochemical properties. We observed that N enrichment individually or in combination with P enrichment, escalated N2O emissions. P enrichment dampened the stimulatory effect of N enrichment on N2O emissions, indicative of an antagonistic effect. Structural equation modeling (SEM) revealed that N enrichment enhanced N2O emissions through alterations in fungal community composition and key soil physicochemical properties such as pH, ammonium nitrogen (NH4+-N), available phosphorus (AP), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN)). Notably, our findings demonstrated that N2O emissions were significantly more influenced by fungal activities, particularly genera like Fusarium, rather than bacterial processes in response to N enrichment. Overall, the study highlights that N enrichment intensifies the role of fungal attributes and soil properties in driving N2O emissions. In contrast, P enrichment exhibited a non-significant effect on N2O emissions, which highlights the critical role of the fungal community in N2O emissions responses to nutrient enrichments in alpine grassland ecosystems.

Case report: A case of brucellosis misdiagnosed as coronavirus disease 2019/influenza in China.

Brucellosis is an important zoonosis and a multisystem disease. The signs and symptoms of brucellosis are not specific. In the clinical, brucellosis is often ignored and misdiagnosed. We report a case of brucellosis who was misdiagnosed as coronavirus disease 2019 (COVID-19)/influenza and received delayed treatment during strict COVID-19 control. The neglect of other diseases due to COVID-19 and empirical diagnosis and treatment by medical staff are part of the reasons for misdiagnosis. Otherwise, the normal erythrocyte sedimentation rate (ESR), increased white blood cell count (WBC), and increased neutrophil count (NEUT) of this patient was also a cause of misdiagnosis, which is an important reminder for diagnosis. For patients with the unknown origin of fever and other symptoms related to brucellosis, especially those from endemic areas of brucellosis, brucellosis screening is a priority item, and grassroots doctors should be vigilant and standardize the diagnosis and treatment based on epidemiology history, clinical manifestation, and laboratory tests according to the diagnostic criteria of brucellosis.

Identification of Novel Bartonella washoensis Sequence Type 22 in Marmota himalayana - Jiuquan City, Gansu Province, China, 2021-2022.

What is already known about this topic?: The prevalence of rodent-adapted Bartonella species has been increasing significantly. However, the specific Bartonella species carried by Marmota himalayana (M. himalayana), a large rodent species, and the potential risk it poses to human populations remain unknown. What is added by this report?: Bartonella washoensis (B. washoensis), associated with human endocarditis, was initially identified in M. himalayana, exhibiting a detection rate of approximately one-third and demonstrating a predilection for the heart and lungs. The discovery of the novel Sequence Type 22 has expanded both the isolation source and genetic lineage of B. washoensis. What are the implications for public health practice?: Individuals residing within the M. himalayana plague focus are at an elevated risk for B. washoensis infection. Consequently, there is a pressing need for public health warnings and efficient clinical case identification in this population.

Case Report: Screening and Analysis for Brucellosis in Akesai Kazak Autonomous County, China.

Brucellosis is a common zoonotic disease. For this study, the residents of Akesai Kazak Autonomous County, located in the high altitude of the Altun Mountains region of Gansu Province, were selected. These people rely on traditional animal husbandry for their main income. The prevalence of brucellosis and the change of antibody titer in this high-risk population were analyzed, and information on the epidemic in animals in the county was obtained from data records. One hundred ninety-nine persons were screened and 240 serum samples were collected. Eight persons and 27 serum samples were positive based on the rose bengal plate test, and seven persons were confirmed positive by standard agglutination test; 16,000 sheep were tested, of which 130 from nine different households were serum antibody positive. The results indicate that brucellosis seroprevalence increased among sheep and high-risk populations, and the occurrence of cases corresponded to the epidemic among animals. The incidence of human brucellosis was closely related to occupation, and the cases were mainly distributed among herdsmen and butchers. Most cases were asymptomatic or mild, and the serum antibody titers showed a high initial titer but a rapid decline in young cases, whereas those in older cases were relatively low but showed a slow decline.

Aboveground herbivory can promote exotic plant invasion through intra- and interspecific aboveground-belowground interactions.

Aboveground herbivores and soil biota profoundly affect plant invasions. However, how they interactively affect plant invasions through plant-soil feedbacks (PSFs) remains unclear. To explore how herbivory by the introduced beetle Agasicles hygrophila affects Alternanthera philoxeroides invasions in China, we integrated multiyear field surveys and a 2-yr PSF experiment, in which we examined how herbivory affects PSFs on the performance of native and invasive plants and the introduced beetles. Despite increased herbivory from A. hygrophila, A. philoxeroides dominance over co-occurring congeneric native Alternanthera sessilis remained constant from 2014 to 2019. While occurring at lower abundances, A. sessilis experienced similar herbivore damage, suggesting apparent competitive effects. Our experiments revealed that herbivory on A. philoxeroides altered soil microbial communities, prolonged its negative PSF on A. sessilis, and decreased A. hygrophila larvae performance on the next-generation invasive plants. Consequently, A. hygrophila larvae performed better on leaves of natives than those of invasives when grown in soils conditioned by invasive plants defoliated by the introduced beetles. Our findings suggest that aboveground herbivory might promote rather than suppress A. philoxeroides invasion by enhancing its soil-mediated self-reinforcement, providing a novel mechanistic understanding of plant invasions. These findings highlight the need to incorporate an aboveground-belowground perspective during the assessment of potential biocontrol agents.

Metabolism and residue differences of Enrofloxacin between the brain and peripheral tissues and the resulting brain damages in crucian carp (Carassius auratus var. Pengze).

This study aimed to explore the metabolism and residue differences of Enrofloxacin (ENR) at two doses between the brain and peripheral tissues (liver, kidney, and muscle) along with the brain damages caused by ENR in crucian carp (Carassius auratus var. Pengze). The concentrations of ENR in tissues were determined using a validated high-performance liquid chromatography (HPLC) analysis. Relying on the hematoxylin-eosin (HE) staining method, brain damages caused by the drug were evaluated by the section of pathological tissue. Metabolism and residue results showed that ENR could be detected in the brain throughout the experiment both at median lethal dose (LD50 at 96 h, 1949.84 mg/kg) and safe dose (SD, 194.98 mg/kg), as well as in the three peripheral tissues. The maximum residue at LD50 followed the decreasing order of liver >kidney > brain > muscle. Although the Cmax of ENR at SD in the brain was significantly lower than that in other peripheral tissues (p < .05), it still reached 41.91 µg/g. The T1/2 of ENR in brain tissue at the same dose was both shorter than that in peripheral tissues. At LD50 , the amount of ENR residues in brain was lower than that in peripheral tissues on the whole, except that it had been higher than in the muscle for the first 3 h. At SD, the drug residue in brain tissue was lower than that in peripheral tissues from 12 h to 960 h, but it exceeded the muscle and kidney at 1 h and 6 h, respectively. At 960 h, the residual amount of ENR at SD in the brain was 0.09 µg/g, while it was up to 0.15 µg/g following the oral administration at LD50 . Demonstrated by the HE staining, there were pathological lesions caused by ENR in the brain at LD50 , which were characterized by sparse neural network and increased staining of glial cells. The present results indicated that metabolism and residue of ENR in crucian carp were affected by the tissue type and drug dosage, and the ENR could also bring about histopathological changes in the brain.

Serological investigation of plague and brucellosis infection in Marmota himalayana plague foci in the Altun Mountains on the Qinghai-Tibet Plateau.

The Altun Mountains are among the most active regions of Marmota himalayana plague foci of the Qinghai-Tibet Plateau where animal plague is prevalent, whereas only three human cases have been found since 1960. Animal husbandry is the main income for the local economy; brucellosis appears sometimes in animals and less often in humans. In this study, a retrospective investigation of plague and brucellosis seroprevalence among humans and animals was conducted to improve prevention and control measures for the two diseases. Animal and human sera were collected for routine surveillance from 2018 to 2021 and screened for plague and brucellosis. Yersinia pestis F1 antibody was preliminarily screened by the colloidal gold method at the monitoring site to identify previous infections with positive serology. Previous plague infection was found in 3.2% (14/432) of the studied human population having close contact with livestock, which indicates evidence of exposure to the Yersinia antigen (dead or live pathogenic materials) in the Altun Mountains. Seroprevalence of brucellosis was higher in camels (6.2%) and sheepdogs (1.8%) than in other livestock such as cattle and sheep, suggesting a possible transmission route from secondary host animals to humans.

Soil properties rather than plant diversity mediate the response of soil bacterial community to N and P additions in an alpine meadow.

The alpine meadow on the Qinghai-Tibetan Plateau, which is susceptible to global climate change and human activities, is subject to nutrient addition such as nitrogen (N) and phosphorus (P) to enhance soil available nutrients and ecosystem productivity. Soil bacterial community partly drivers the effects of nutrient additions on ecosystem processes, whereas the factors influencing N and P additions on bacterial community in alpine meadows are not well documented. We conducted a N and P addition experiment in an alpine meadow ecosystem on the Qinghai-Tibetan Plateau with four treatments: untreated control (CK), N addition (N), P addition (P), and NP addition (NP). We employed a high-throughput Illumina Miseq sequencing technology to investigate the response of soil bacterial community to short-term N and P additions. N and P additions decreased soil bacterial richness (OTU numbers and Chao 1 index), and P addition decreased soil bacterial diversity (Shannon and Simpson indices). N addition directly induced the change of soil N H 4 + - N , and decreased plant diversity. The N and P additions reduced soil bacterial community diversity, whose response was independent with plant diversity. Additionally, nutrient additions altered soil bacterial community composition, which were highly correlated with soil properties (i.e. pH, N H 4 + - N , and TP) as shown by RDA. Consistently, structural equation modeling results revealed that N addition indirectly acted on soil bacterial community through altering soil available nutrients and pH, while P addition indirectly affected bacterial community by increasing soil P availability. These findings imply that more attention should be paid to soil properties in regulating belowground biodiversity process in alpine meadows under future environmental change scenario.

Plague Outbreak of a Marmota himalayana Family Emerging from Hibernation.

In April 2021, a plague outbreak was identified within one Marmota himalayana family shortly after emerging from hibernation, during plague surveillance in the M. himalayana plague foci of the Qinghai-Tibet Plateau. A total of five marmots were found dead of Yersinia pestis near the same burrow; one live marmot was positive of Y. pestis fraction 1 (F1) antibody. Comparative genome analysis shows that few single nucleotide polymorphisms were detected among the nine strains, indicating the same origin of the outbreak. The survived marmot shows a high titer of F1 antibody, higher than the mean titer of all marmots during the 2021 monitoring period (W = 391.00, Z = 2.81, p < 0.01). Marmots live with Y. pestis during hibernation when the pathogen is inhibited by hypothermia. But they wake up during or just after hibernation with body temperature rising to 37°C, when Y. pestis goes through optimal growth temperature, increases virulence, and causes death in marmots. A previous report has shown human plague cases caused by excavating marmots during winter; combined, this study shows the high risk of hibernation marmot carrying Y. pestis. This analysis provides new insights into the transmission of the highly virulent Y. pestis in M. himalayana plague foci and drives further effort upon plague control during hibernation.

Anaplasma phagocytophilum in Marmota himalayana.

BACKGROUND: Human granulocytic anaplasmosis is a tick-borne zoonotic disease caused by Anaplasma phagocytophilum. Coinfections with A. phagocytophilum and other tick-borne pathogens are reported frequently, whereas the relationship between A. phagocytophilum and flea-borne Yersnia pestis is rarely concerned. RESULTS: A. phagocytophilum and Yersnia pestis were discovered within a Marmota himalayana found dead in the environment, as determined by 16S ribosomal rRNA sequencing. Comparative genomic analyses of marmot-derived A. phagocytophilum isolate demonstrated its similarities and a geographic isolation from other global strains. The 16S rRNA gene and GroEL amino acid sequence identity rates between marmot-derived A. phagocytophilum (JAHLEX000000000) and reference strain HZ (CP000235.1) are 99.73% (1490/1494) and 99.82% (549/550), respectively. 16S rRNA and groESL gene screenings show that A. phagocytophilum is widely distributed in marmots; the bacterium was more common in marmots found dead (24.59%, 15/61) than in captured marmots (19.21%, 29/151). We found a higher Y. pestis isolation rate in dead marmots harboring A. phagocytophilum than in those without it (2 = 4.047, p < 0.05). Marmot-derived A. phagocytophilum was able to live in L929 cells and BALB/c mice but did not propagate well. CONCLUSIONS: In this study, A. phagocytophilum was identified for the first time in Marmota himalayana, a predominant Yersinia pestis host. Our results provide initial evidence for M. himalayana being a reservoir for A. phagocytophilum; moreover, we found with the presence of A. phagocytophilum, marmots may be more vulnerable to plague. Humans are at risk for co-infection with both pathogens by exposure to such marmots.

A Lytic Yersina pestis Bacteriophage Obtained From the Bone Marrow of Marmota himalayana in a Plague-Focus Area in China.

A lytic Yersinia pestis phage vB_YpP-YepMm (also named YepMm for briefly) was first isolated from the bone marrow of a Marmota himalayana who died of natural causes on the Qinghai-Tibet plateau in China. Based on its morphologic (isometric hexagonal head and short non-contractile conical tail) and genomic features, we classified it as belonging to the Podoviridae family. At the MOI of 10, YepMm reached maximum titers; and the one-step growth curve showed that the incubation period of the phage was about 10 min, the rise phase was about 80 min, and the lysis amount of the phage during the lysis period of 80 min was about 187 PFU/cell. The genome of the bacteriophage YepMm had nucleotide-sequence similarity of 99.99% to that of the Y. pestis bacteriophage Yep-phi characterized previously. Analyses of the biological characters showed that YepMm has a short latent period, strong lysis, and a broader lysis spectrum. It could infect Y. pestis, highly pathogenic bioserotype 1B/O:8 Y. enterocolitica, as well as serotype O:1b Y. pseudotuberculosis-the ancestor of Y. pestis. It could be further developed as an important biocontrol agent in pathogenic Yersinia spp. infection.

Latitudinal variation in the diversity and composition of various organisms associated with an exotic plant: the role of climate and plant invasion.

Climate and plant invasion can shape biotic communities at large spatial scales. Yet, how diverse groups of organisms associated with an invasive plant change simultaneously with latitude and the roles of climate and plant invasion remains unclear. We conducted a field survey of plants (native vs exotic), soil fungi (pathogenic, saprotrophic, arbuscular mycorrhiza fungi (AMF) and ectomycorrhizal (EcM) fungi) and arthropods (herbivores, predators and detritivores) associated with the invasive plant Alternanthera philoxeroides at 49 sites spanning 14 latitudinal degrees in China. Results showed that diversity and composition of these functional groups changed differently with latitude, partially due to their specific responses to climate, invasion of A. philoxeroides and other biotic environments. Moreover, A. philoxeroides invasion and/or composition of other plants, rather than climate, predicted the diversity and richness of major functional groups and partly explained variance in composition of putative fungal pathogens. Our results suggest that climate and plant invasion could affect the diversity and composition of diverse groups of organisms simultaneously and their relative importance might vary among functional groups. Thus, it is necessary to explore latitudinal patterns and underlying drivers of diverse groups of organisms simultaneously to improve our ability to predict and mitigate threats posed by plant invasion and climate change.

Plant evolution overwhelms geographical origin in shaping rhizosphere fungi across latitudes.

As the number of non-native invasive species in the world is increasing, there is a pressing need to understand the effects of invasive species on recipient biotic communities to improve our ability to migrate or relieve their potential negative effects on biodiversity and ecosystem functions. Plant invasions have been shown to impose great threats to aboveground biotic communities; however, invasive impacts on soil biota remain ambiguous, partially because of the paucity of studies with a large number of species across biogeographic gradients. Here, we characterized rhizosphere fungal communities of 53 native and invasive plants spanning approximately 1800 km in China, as well as eight pairs of phylogenetically related native versus invasive plants in a greenhouse experiment. The results of both field survey and greenhouse experiment showed that rhizosphere fungal composition was primarily predicted by plant phylogeny (e.g. family and species), and plant geographic origin (native vs. invasive) and abiotic factors had much smaller effects. We detected no differences in the number and relative abundance of total and family/species-specific OTUs (i.e. overall, pathogens and mutualists) associated with these native and invasive plants on average, suggesting novel co-evolution between native soil fungi and these invasive plants. These results suggest that non-native plant invasions had only a weak impact on soil fungi, partially due to stronger controls of plant evolution on rhizosphere fungi and adaptation of native fungi to these invasive species. Interestingly, rhizosphere fungal composition was more variable between invasive plants than between native plants at middle latitudes, potentially creating spatial variations in plant-soil interactions and, in turn, invasion dynamics. These novel findings highlight the importance of integrating phylogenetic and biogeographical approaches to explore invasive effects on native biota.

An invasive plant rapidly increased the similarity of soil fungal pathogen communities.

BACKGROUND AND AIMS: Plant invasions can change soil microbial communities and affect subsequent invasions directly or indirectly via foliar herbivory. It has been proposed that invaders promote uniform biotic communities that displace diverse, spatially variable communities (the biotic homogenization hypothesis), but this has not been experimentally tested for soil microbial communities, so the underlying mechanisms and dynamics are unclear. Here, we compared density-dependent impacts of the invasive plant Alternanthera philoxeroides and its native congener A. sessilis on soil fungal communities, and their feedback effects on plants and a foliar beetle. METHODS: We conducted a plant-soil feedback (PSF) experiment and a laboratory bioassay to examine PSFs associated with the native and invasive plants and a beetle feeding on them. We also characterized the soil fungal community using high-throughput sequencing. KEY RESULTS: We found locally differentiated soil fungal pathogen assemblages associated with high densities of the native plant A. sessilis but little variation in those associated with the invasive congener A. philoxeroides, regardless of plant density. In contrast, arbuscular mycorrhizal fungal assemblages associated with high densities of the invasive plant were more variable. Soil biota decreased plant shoot mass but their effect was weak for the invasive plant growing in native plant-conditioned soils. PSFs increased the larval biomass of a beetle reared on leaves of the native plant only. Moreover, PSFs on plant shoot and root mass and beetle mass were predicted by different pathogen taxa in a plant species-specific manner. CONCLUSION: Our results suggest that plant invasions can rapidly increase the similarity of soil pathogen assemblages even at low plant densities, leading to taxonomically and functionally homogeneous soil communities that may limit negative soil effects on invasive plants.

Herbivory may promote a non-native plant invasion at low but not high latitudes.

BACKGROUND AND AIMS: The strengths of biotic interactions such as herbivory are expected to decrease with increasing latitude for native species. To what extent this applies to invasive species and what the consequences of this variation are for competition among native and invasive species remain unexplored. Here, herbivore impacts on the invasive plant Alternanthera philoxeroides and its competition with the native congener A. sessilis were estimated across latitudes in China. METHODS: An common garden experiment spanning ten latitudinal degrees was conducted to test how herbivore impacts on A. philoxeroides and A. sessilis, and competition between them change with latitude. In addition, a field survey was conducted from 21°N to 36.8°N to test whether A. philoxeroides invasiveness changes with latitude in nature as a result of variations in herbivory. KEY RESULTS: In the experiment, A. sessilis cover was significantly higher than A. philoxeroides cover when they competed in the absence of herbivores, but otherwise their cover was comparable at low latitude. However, A. philoxeroides cover was always higher on average than A. sessilis cover at middle latitude. At high latitude, only A. sessilis emerged in the second year. Herbivore abundance decreased with latitude and A. philoxeroides emerged earlier than A. sessilis at middle latitude. In the field survey, the ratio of A. philoxeroides to A. sessilis cover was hump shaped with latitude. CONCLUSION: These results indicate that herbivory may promote A. philoxeroides invasion only at low latitude by altering the outcome of competition in favour of the invader and point to the importance of other factors, such as earlier emergence, in A. philoxeroides invasion at higher latitudes. These results suggest that the key factors promoting plant invasions might change with latitude, highlighting the importance of teasing apart the roles of multiple factors in plant invasions within a biogeographic framework.

Latitudinal variation in soil biota: testing the biotic interaction hypothesis with an invasive plant and a native congener.

Soil biota community structure can change with latitude, but the effects of changes on native plants, invasive plants, and their herbivores remain unclear. Here, we examined latitudinal variation in the soil biota community associated with the invasive plant Alternanthera philoxeroides and its native congener A. sessilis, and the effects of soil biota community variation on these plants and the beetle Agasicles hygrophila. We characterized the soil bacterial and fungal communities and root-knot nematodes of plant rhizospheres collected from 22 °N to 36.6 °N in China. Soil biota community structure changed with latitude as a function of climate and soil properties. Root-knot nematode abundance and potential soil fungal pathogen diversity (classified with FUNGuild) decreased with latitude, apparently due to higher soil pH and lower temperatures. A greenhouse experiment and lab bioassay showed native plant mass, seed production, and mass of beetles fed native foliage increased with soil collection latitude. However, there were no latitudinal patterns for the invasive plant. These results suggest that invasive and native plants and, consequently, their herbivores have different responses to latitudinal changes in soil-borne enemies, potentially creating spatial variation in enemy release or biotic resistance. This highlights the importance of linking above- and below-ground multitrophic interactions to explore the role of soil biota in non-native plant invasions with a biogeographic approach.

Inhibition of Mitochondrial Fission Preserves Photoreceptors after Retinal Detachment.

Photoreceptor degeneration is a leading cause of visual impairment worldwide. Separation of neurosensory retina from the underlying retinal pigment epithelium is a prominent feature preceding photoreceptor degeneration in a variety of retinal diseases. Although ophthalmic surgical procedures have been well developed to restore retinal structures, postoperative patients usually experience progressive photoreceptor degeneration and irreversible vision loss that is incurable at present. Previous studies point to a critical role of mitochondria-mediated apoptotic pathway in photoreceptor degeneration, but the upstream triggers remain largely unexplored. In this study, we show that after experimental retinal detachment induction, photoreceptors activate dynamin-related protein 1 (Drp1)-dependent mitochondrial fission pathway and subsequent apoptotic cascades. Mechanistically, endogenous reactive oxygen species (ROS) are necessary for Drp1 activation in vivo, and exogenous ROS insult is sufficient to activate Drp1-dependent mitochondrial fission in cultured photoreceptors. Accordingly, inhibition of Drp1 activity effectively preserves mitochondrial integrity and rescues photoreceptors. Collectively, our data delineate an ROS-Drp1-mitochondria axis that promotes photoreceptor degeneration in retinal diseased models.

Choroidal pericytes promote subretinal fibrosis after experimental photocoagulation.

Subretinal fibrosis results in local destruction of retinal structures and permanent vision loss, representing the end stage of neovascular age-related macular degeneration (AMD). Histological examination of fibrotic specimens from AMD patients has uncovered a wide range of cellular and acellular components. However, their origins and roles in fibrosis remain largely unexplored. Using a laser-induced photocoagulation model with collagen 1α1-GFP reporter mice, we demonstrate, by cell-lineage tracing, that pericytes associating with choroidal microvasculature are activated upon injury and infiltrate into the subretinal space as significant components of fibrotic lesions. In contrast to their choroidal precursors, infiltrating pericytes acquire stellate-like structures, upregulate expression of fibrogenic molecules and colocalize with extracellular fibrotic scar. Collectively, our results identify the choroidal perivascular niche as a novel source of subretinal fibrosis after photocoagulation, and suggest that collagen 1-expressing pericytes are potential targets for therapeutic intervention to suppress subretinal fibrosis and preserve vision.