RESUMEN
Inflammasome involvement in Parkinson's disease (PD) has been intensively investigated. Absent in melanoma 2 (AIM2) is an essential inflammasome protein known to contribute to the development of several neurological diseases. However, a specific role for AIM2 in PD has not been reported. In this study, we investigated the effect of AIM2 in the N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model by use of various knockout and bone marrow chimeric mice. The mechanism of action for AIM2 in PD was assessed by RNA-sequencing and in vitro primary microglial transfection. Results were validated in the A30P transgenic mouse model of PD. In the MPTP mouse model, AIM2 activation was found to negatively regulate neuro-inflammation independent of the inflammasome. Microglial AIM2 deficiency exacerbated behavioral and pathological features of both MPTP-induced and transgenic PD mouse models. Mechanistically, AIM2 reduced cyclic GMP-AMP synthase (cGAS)-mediated antiviral-related inflammation by inhibition of AKT-interferon regulatory factor 3 (IRF3) phosphorylation. These results demonstrate microglial AIM2 to inhibit the antiviral-related neuro-inflammation associated with PD and provide for a foundation upon which to identify new therapeutic targets for treatment of the disease.
Asunto(s)
Melanoma , Enfermedad de Parkinson , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Antivirales/farmacología , Proteínas de Unión al ADN , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/metabolismo , Inflamasomas/metabolismo , Inflamación/metabolismo , Factor 3 Regulador del Interferón/metabolismo , Factor 3 Regulador del Interferón/farmacología , Melanoma/metabolismo , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microglía/metabolismo , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirrolidinas/metabolismo , Pirrolidinas/farmacología , ARN/metabolismoRESUMEN
OBJECTIVES: To explore the application values of diatom artificial intelligence (AI) search system in the diagnosis of drowning. METHODS: The liver and kidney tissues of 12 drowned corpses were taken and were performed with the diatom test, the view images were obtained by scanning electron microscopy (SEM). Diatom detection and forensic expert manual identification were carried out under the thresholds of 0.5, 0.7 and 0.9 of the diatom AI search system, respectively. Diatom recall rate, precision rate and image exclusion rate were used to detect and compare the efficiency of diatom AI search system. RESULTS: There was no statistical difference between the number of diatoms detected in the target marked by the diatom AI search system and the number of diatoms identified manually (P>0.05); the recall rates of the diatom AI search system were statistically different under different thresholds (P<0.05); the precision rates of the diatom AI system were statistically different under different thresholds(P<0.05), and the highest precision rate was 53.15%; the image exclusion rates of the diatom AI search system were statistically different under different thresholds (P<0.05), and the highest image exclusion rate was 99.72%. For the same sample, the time taken by the diatom AI search system to identify diatoms was only 1/7 of that of manual identification. CONCLUSIONS: Diatom AI search system has a good application prospect in drowning cases. Its automatic diatom search ability is equal to that of experienced forensic experts, and it can greatly reduce the workload of manual observation of images.
Asunto(s)
Diatomeas , Ahogamiento , Inteligencia Artificial , Ahogamiento/diagnóstico , Humanos , Hígado , Pulmón , Microscopía Electrónica de RastreoRESUMEN
Cadmium (Cd) exposure is harmful to amphibians in natural environments and the Cd concentration is a key parameter in water monitoring. Cd pollution has been a severe issue in the Yangtze River and its southern reaches in recent years. Acute toxicity assays were employed to determine the tolerance limits of Cd for Microhyla fissipes tadpoles and five different concentrations of Cd (0, 50, 100, 200 and 300 µg/L) were involved to detect its chronic effects on metamorphosis, growth, locomotion, genotoxicity and enzymatic activities of M. fissipes tadpoles. The results showed that the 24-h and 48-h LC50 values of Cd on M. fissipes tadpoles were 2591.3 µg/L and 1567.9 µg/L, respectively, and the presumable non-lethal concentration obtained was 172.2 µg/L. During the 70-day chronic toxicity assays, Cd showed negative impacts on survival, growth, metamorphosis and the frequency of erythrocytes nuclear abnormality of M. fissipes tadpoles. However, the Cd exposure caused the increased body size and condition of tadpoles at complete metamorphosis (GS46). The tadpoles exposed to 200 µg/L of Cd exhibited degraded locomotor performance at GS46. Weight increments of tadpoles were inhibited at Day 14 and massive deaths were observed over the next 14 days. The enzymatic activities of tadpoles experienced a shock response stage (GS30-GS35) and a complete recovery stage (GS36-GS41) in all treatments. However, the enzymatic activities (except alkaline phosphatase) of tadpoles at GS46 increased after Cd exposure, especially at high concentrations. In summary, Cd is a threat to M. fissipes tadpoles as that causes reduced fitness.
Asunto(s)
Anuros/fisiología , Cadmio/toxicidad , Locomoción/efectos de los fármacos , Metamorfosis Biológica/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Anuros/crecimiento & desarrollo , Larva/efectos de los fármacos , Larva/enzimología , Dosificación Letal MedianaRESUMEN
Inter-population variations in growth rate can result from independent or interactive effects of genetic and environmental factors, and be induced by some physiological differences as well. Toad-headed lizards (Phrynocephalus vlangalii) from a higher-elevation population were shown to have a higher growth rate than those from a lower-elevation population. The physiological basis of growth rate variation in this species is not well understood. Here, we investigated the feeding performance and resting metabolic rate (RMR) of lower- and higher-elevation individuals at different test ambient temperatures to evaluate the role of differences in energy intake, assimilation efficiency and metabolic expenditure on growth rate variations. Within the range of 25-35⯰C, lizard RMR increased with increasing test ambient temperature, but food intake, apparent digestive coefficient (ADC, food energy minus faecal energy divided by food energy), and assimilation efficiency (AE, food energy minus faecal and urinary energy divided by food energy) were less thermally sensitive in both populations. Higher-elevation lizards tended to eat more food and have a lower RMR than lower-elevation ones, despite the lack of differences in ADC and AE. Our result showed that more energy intake and reduced maintenance cost may be associated with the higher growth rate of higher-elevation lizards. Accordingly, inter-population differences in energy acquisition and expenditure could act as potential sources for geographic variation in growth rate.
Asunto(s)
Altitud , Lagartos/fisiología , Animales , Metabolismo Basal , Ingestión de Alimentos , MasculinoRESUMEN
Population differentiation in ectotherm physiological performance may be driven by adapting to different thermal environments. In this study, we measured locomotor performance in two different altitude populations of the Qinghai toad-headed lizards (Phrynocephalus vlangalii) at different test temperatures to assess between-population differences in thermal sensitivity of sprint speed. Low-elevation lizards ran faster than high-elevation lizards at most test temperatures. Sprint speed varied with test temperature similarly between populations, but the thermal sensitivity (performance breadth) differed significantly. Low-elevation lizards had a lower optimal temperature (Topt) for sprint speed and narrower performance breadth than high-elevation lizards as inferred from the thermal performance curves constructed for each individual. We also measured the body temperature of active lizards (Tb) in the field and selected temperature (Tsel) in the laboratory. Low-elevation lizards had a lower Tsel, and less variable Tb than high-elevation lizards. In both populations, Tsel was lower than Topt for sprint speed, which was inconsistent with the prediction for a match between thermal preference and Topt. Our results suggest that lower thermal sensitivity and weaker locomotor ability for high-elevation lizards may be an adaptive response to the local environmental conditions (e.g., greater thermal variability, higher food availability, and lower predator pressure).
Asunto(s)
Altitud , Temperatura Corporal , Lagartos/fisiología , Locomoción , Aclimatación , AnimalesRESUMEN
The thermal physiological performance of invasive species may play a crucial role in determining their invasion success. In this study, we acclimated two cohorts of hatchlings of freshwater turtles (native Mauremys reevesii and invasive Trachemys scripta elegans) from low and high-latitude collection sites, respectively, to different thermal conditions (20 and 30 °C) for 4 weeks, and then compared their thermal tolerance and locomotor performance. T. scripta elegans hatchlings could swim faster (but righted themselves more slowly), and tolerate a higher temperature and wider temperature range than M. reevesii hatchlings. Similarly, T. scripta elegans hatchlings had a greater maximal performance (Pmax) value for swimming speed (but a lower Pmax value for righting time) than M. reevesii hatchlings. Temperature acclimation had a significant impact on the thermal tolerance and locomotor ability of turtles, but the acclimation effect did not differ between the two species. T. scripta elegans hatchlings seemed to have a greater thermal plasticity than M. reevesii hatchlings. High-latitude individuals showed a greater low-temperature tolerance, but lower locomotor ability (longer righting time) than low-latitude ones. However, the thermal plasticity did not differ between latitudinal cohorts. Our results indicated that T. scripta elegans performed better than M. reevesii, which might contribute to its range expansion and invasive success.
Asunto(s)
Temperatura , Termotolerancia , Tortugas/fisiología , Animales , Agua Dulce , Natación/fisiologíaRESUMEN
BACKGROUND: Previous studies investigating the association between altered long noncoding RNAs (lncRNAs) and survival outcomes in ovarian cancer have obtained controversial results. To comprehensively evaluate the association, we conducted a systematic review and meta-analysis of the studies published on the subject. METHODS: We performed a systematic search using the databases of the Cochrane Central Register of Controlled Trials, PubMed, and Embase to find all relevant articles from inception to May 7, 2017. Studies that evaluated the association between 1 specific lncRNA and survival outcomes in ovarian cancer were included. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) for overall survival, progression-free survival, and disease-free survival were calculated with a fixed-effects or random-effects model. RESULTS: A total of 15 studies involving 1333 patients with ovarian cancer were included in this meta-analysis. Altered lncRNAs were associated with decreased overall survival (HR: 2.29, 95% CI: 1.92-2.75) without heterogeneity (Iâ=â0.0%) in ovarian cancer. Altered lncRNAs were also associated with decreased progression-free survival (HR: 2.77, 95% CI: 1.00-7.62, Iâ=â76.6%) and disease-free survival (HR: 2.59, 95% CI: 0.89-7.57, Iâ=â62.9%) in ovarian cancer. CONCLUSION: Our results supported the strong prognostic value of altered lncRNAs in ovarian cancer. Further large-scale studies should be carried out to verify the clinical applications of altered lncRNAs in the prognosis assessment of ovarian cancer.
Asunto(s)
Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , ARN Largo no Codificante/análisis , Biomarcadores de Tumor/análisis , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
In reptiles, habitat selection is the process whereby suitable habitat is selected that optimizes physiological functions and behavioral performance. Here, we used the brown forest skink (Sphenomorphus indicus) as a model animal and examined whether the frequency of active individuals, environmental temperature, illumination of activity area, and habitat type vary with different age classes. We surveyed the number of active individuals and measured environmental variables at Baiyunshan Mountain in Lishui, Zhejiang, China. We found no difference in the activity frequency of adult and juvenile S. indicus; the activity pattern of active individuals was bimodal. The mean environmental temperature selected by adults was higher than that selected by juveniles. The environmental temperature of active areas measured at 0900-1000 h and 1100-1200 h was higher than at 1400-1500 h; illumination of the active area at 1000-1200 h was also higher than at 1400 h-1600 h. The number of active individuals, the environmental temperature and illumination of activity areas showed pairwise positive correlation. There was a difference in habitat type between juveniles and adults whereby juveniles prefer rock habitats. We predict that active S. indicus select optimal habitats with different environmental temperatures and types to reach the physiological needs particular to their age classes.