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Chronic stress may induce learning and memory deficits that are associated with a depression-like state in Drosophila melanogaster. The molecular and neural mechanisms underlying the etiology of chronic stress–induced learning deficit (CSLD) remain elusive. Here, we show that the autophagy-lysosomal pathway, a conserved cellular signaling mechanism, is associated with chronic stress in Drosophila, as indicated by time-series transcriptome profiling. Our findings demonstrate that chronic stress induces the disruption of autophagic flux, and chronic disruption of autophagic flux could lead to a learning deficit. Remarkably, preventing the disruption of autophagic flux by up-regulating the basal autophagy level is sufficient to protect against CSLD. Consistent with the essential role of the dopaminergic system in modulating susceptibility to CSLD, dopamine neuronal activity is also indispensable for chronic stress to induce the disruption of autophagic flux. By screening knockout mutants, we found that neuropeptide F, the Drosophila homolog of neuropeptide Y, is necessary for normal autophagic flux and promotes resilience to CSLD. Moreover, neuropeptide F signaling during chronic stress treatment promotes resilience to CSLD by preventing the disruption of autophagic flux. Importantly, neuropeptide F receptor activity in dopamine neurons also promotes resilience to CSLD. Together, our data elucidate a mechanism by which stress-induced excessive dopaminergic activity precipitates the disruption of autophagic flux, and chronic disruption of autophagic flux leads to CSLD, while inhibitory neuropeptide F signaling to dopamine neurons promotes resilience to CSLD by preventing the disruption of autophagic flux. [ABSTRACT FROM AUTHOR]

Biological effects of magnetic fields have been extensively studied in plants, microorganisms and animals, and applications of magnetic fields in regulation of plant growth and phytoprotection is a promising field in sustainable agriculture. However, the effect of magnetic fields especially ultra-high static magnetic field (UHSMF) on genomic stability is largely unclear. Here, we investigated the mutagenicity of 24.5, 30.5 and 33.0 T UHSMFs with the gradient of 150, 95 and 0 T/m, respectively, via whole genome sequencing. Our results showed that 1 h exposure of Arabidopsis dried seeds to UHSMFs has no significant effect on the average rate of DNA mutations including single nucleotide variations and InDels (insertions and deletions) in comparison with the control, but 33.0 T and 24.5 T treatments lead to a significant change in the rate of nucleotide transitions and InDels longer than 3 bp, respectively, suggesting that both strength and gradient of UHSMF impact molecular spectrum of DNA mutations. We also found that the decreased transition rate in UHSMF groups is correlated with the upstream flanking sequences of G and C mutation sites. Furthermore, the germination rate of seeds exposed to 24.5 T SMF with -150 T/m gradient showed a significant decrease at 24 hours after sowing. Overall, our data lay a basis for precisely assessing the potential risk of UHSMF on DNA stability, and for elucidating molecular mechanism underlying gradient SMF-regulated biological processes in the future. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy (RT) is a standard treatment for the local control of primary pelvic cancers (PPC), yet the risk of second corpus uteri cancer (SCUC) in PPC patients undergoing RT is still controversial. This study investigated the impact of RT on the risk of SCUC and assessed the survival outcome. Methods: We queried nine cancer registries for PPC cases in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of SCUC was analyzed using Cox regression and Fine-Gray competing risk regression analysis. The Poisson regression analysis was employed to assess the standardized incidence ratios (SIRs) and radiation-attributed risk (RR) for SCUC. We evaluated the overall survival of patients with SCUC using the Kaplan-Meier method. Results: Receiving radiotherapy was strongly associated with a higher risk of developing SCUC for PPC patients in Fine-Gray competing risk regression (No-RT vs. RT: adjusted HR = 1.77; 95% CI, 1.40-2.28; p < 0.001). The incidence of SCUC in PPC patients who received RT was higher than in the US general population (SIR, 1.66; 95% CI, 1.41-1.93; p < 0.05), but the incidence of SCUC in patients who did not receive RT was lower than with the US general population (SIR, 0.68; 95% CI, 0.61-0.75; p < 0.05). The dynamic SIR and RR for SCUC decreased with decreasing age at PPC diagnosis and decreased with time progress. In terms of overall survival, 10-year survival rates with SCUC after No-RT (NRT) and SCUC after RT were 45.9% and 25.9% (HR = 1.82; 95% CI, 1.46-2.29; p < 0.001), respectively. Conclusion: Radiotherapy for primary pelvic cancers is associated with a higher risk of developing SCUC than patients unexposed to radiotherapy. We suggest that patients with pelvic RT, especially young patients, should receive longterm monitoring for the risk of developing SCUC. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy (RT) is a crucial modality for the local control of pelvic cancer (PC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. This study aimed to identify the relationship between radiation therapy received for the treatment of primary PC and subsequent secondary bladder cancer (SBC). Methods: The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for PC. Fine-gray competing risk regression and Cox regression analyses were employed to assess the cumulative incidence of SBC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since PC diagnosis, calendar year of PC diagnosis stage, and age at PC diagnosis were also performed. Overall survival (OS) was compared among different treatment groups with SBC by Kaplan--Meier analysis. Results: A total of 318,165 observations showed that the primary cancers were located in pelvic cavity, 256,313 patients did not receive radiation therapy (NRT), 51,347 patients who underwent external beam radiation therapy (EBRT), and 10,505 patients receiving a combination of EBRT and brachytherapy (EBRT--BRT) who developed SBC. Receiving two types of radiotherapy was strongly consistent with a higher risk of developing SBC for PC patients in Fine- Gray competing risk regression (NRT vs. EBRT, adjusted HR= 1.71, 95% CI: 1.54-1.90, P<0.001; NRT vs. EBRT--BRT, adjusted HR= 2.16, 95% CI: 1.78-2.63, P<0.001). The results of the dynamic SIR and Poisson regression analysis for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency and was significantly related to the variations of age at PC diagnosis and decreased with time progress. For OS, the SBC after NRT, SBC after EBRT, and SBC after EBRT-BRT of 10-year survival rates were 37.9%, 29.2%, and 22.2%, respectively. Conclusion: Radiotherapy for primary PC was associated with higher risks of developing SBC than patients unexposed to radiotherapy. Different pelvic RT treatment modalities had different effects on the risk of SBC. [ABSTRACT FROM AUTHOR]

Chronic stress could induce severe cognitive impairments. Despite extensive investigations in mammalian models, the underlying mechanisms remain obscure. Here, we show that chronic stress could induce dramatic learning and memory deficits in Drosophila melanogaster. The chronic stress--induced learning deficit (CSLD) is long lasting and associated with other depression-like behaviors. We demonstrated that excessive dopaminergic activity provokes susceptibility to CSLD. Remarkably, a pair of PPL1-γ1pedc dopaminergic neurons that project to the mushroom body (MB) γ1pedc compartment play a key role in regulating susceptibility to CSLD so that stress-induced PPL1-γ1pedc hyperactivity facilitates the development of CSLD. Consistently, the mushroom body output neurons (MBON) of the γ1pedc compartment, MBON-γ1pedc>α/β neurons, are important for modulating susceptibility to CSLD. Imaging studies showed that dopaminergic activity is necessary to provoke the development of chronic stress--induced maladaptations in the MB network. Together, our data support that PPL1-γ1pedc mediates chronic stress signals to drive allostatic maladaptations in the MB network that lead to CSLD. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to investigate the functional role of L1.2, the zebrafish paralog of L1.1 and ortholog of mammalian L1CAM in adult zebrafish spinal cord regeneration after injury. L1CAM and L1.1 have shown beneficial features in ameliorating nervous system dysfunctions in different experimental paradigms. It thus deemed important to characterize the L1.2 member of the L1CAM family, the functions of which are unknown. Methods: Spinal cord transection of adult zebrafish, application of anti-sense morpholino to reduce L1.2 expression, qPCR, immunohistology, immunoblotting, in situ hybridization, retrograde tracing, anterograde tracing. Results: Similar to L1.1, L1.2 expression in adult zebrafish is upregulated after spinal cord transection. By co-localization of in situ hybridization and immunohistology, L1.2 is expressed in neurons and, in contrast to L1.1, it is also expressed in GFAP-immunoreactive glia. Reducing L1.2 protein levels leads to impaired locomotor recovery and reduction of regrowth of severed descending axons from a brain stem nucleus which is composed of neurons innately capable of axonal regrowth. Conclusions: Our findings support the speculation that paralogs of duplicated genes can exert similar functions and may thus represent an advantage over other species that do not carry duplicated genes. [ABSTRACT FROM AUTHOR]