Nonsense-mediated RNA decay (NMD) selectively degrades mutated and aberrantly processed transcripts that contain premature termination codons (PTC). Cellular NMD activity is typically assessed using exogenous PTC-containing reporters. We overcame some inherently problematic aspects of assaying endogenous targets and developed a broadly applicable strategy to reliably and easily monitor changes in cellular NMD activity. Our new method was genetically validated for distinguishing NMD regulation from transcriptional control and alternative splicing regulation, and unexpectedly disclosed a different sensitivity of NMD targets to NMD inhibition. Applying this robust method for screening, we identified NMD-inhibiting stressors but also found that NMD inactivation was not universal to cellular stresses. The high sensitivity and broad dynamic range of our method revealed a strong correlation between NMD inhibition, endoplasmic reticulum (ER) stress, and polysome disassembly upon thapsigargin treatment in a temporal and dose-dependent manner. We found little evidence of calcium signaling mediating thapsigargin-induced NMD inhibition. Instead, we discovered that of the three unfolded protein response (UPR) pathways activated by thapsigargin, mainly protein kinase RNA-like endoplasmic reticulum kinase (PERK) was required for NMD inhibition. Finally, we showed that ER stress compounded TDP-43 depletion in the up-regulation of NMD isoforms that had been implicated in the pathogenic mechanisms of amyotrophic lateral sclerosis and frontotemporal dementia, and that the additive effect of ER stress was completely blocked by PERK deficiency.

The number of people with dementia is increasing rapidly worldwide. Developing strategies to improve quality of life for those with dementia is crucial and is receiving more attention. Natural environments are known for their healing effects on most people. This pilot study aimed to understand the benefits that natural environments, such as gardens, can provide for people with dementia. In total, 42 staff members in nine dementia care facilities were recruited as participants in this study and answered a semistructured questionnaire. One-way analysis of variance with repeated measures and the Mann-Whitney U test were used to compare the effects of garden visits on evaluated characteristics and the differences in evaluated characteristics between free garden use and unfree garden use groups. Data from open-ended questions underwent text analysis to obtain the principal beliefs of the participants. The staff members reported that garden visits had positive effects on mood, social interaction, depression, and agitation in people with dementia because of the multisensory, gentle stimuli of the natural environment. Of the evaluated cognitive characteristics, attention and orientation to time were improved the most after residents with dementia had spent time in a garden. Additionally, staff members in the free garden use group scored the effects of garden visits on the mood, long-term memory, language abilities, spatial ability, aggression, and agitation of patients with dementia as significantly higher than staff members in the unfree garden use group. Recommendations for future studies are discussed.

Ship detection is one of the most important research contents of ship intelligent navigation and monitoring. As a supplement to classical navigational equipment such as radar and the Automatic Identification System (AIS), target detection based on computer vision and deep learning has become a new important method. A target detector called YOLOv3 has the advantages of detection speed and accuracy and meets the real-time requirements for ship detection. However, YOLOv3 has a large number of backbone network parameters and requires high hardware performance, which is not conducive to the popularization of applications. On the basis of YOLOv3, this paper proposes a lightweight ship detection model (LSDM) in which the backbone network is improved by using dense connection inspired from DenseNet, and the feature pyramid networks are improved by using spatial separation convolution to replace normal convolution. The two improvements reduce parameters and optimize the network structure greatly. The experimental results show that, with only one-third of parameters of YOLOv3, the LSDM has higher accuracy and speed for ship detection. In addition, the LSDM is simplified further by reducing the number of densely connected units to form a model called LSDM-tiny. The experimental results show that, LSDM-tiny has similar detection speed with YOLOv3-tiny, but has a lot higher accuracy.

Nonsense-mediated mRNA decay (NMD) degrades transcripts with premature stop codons. Given the prevalence of nonsense single nucleotide polymorphisms (SNPs) in the general population, it is urgent to catalog the effects of clinically approved drugs on NMD activity: any interference could alter the expression of nonsense SNPs, inadvertently inducing adverse effects. This risk is higher for patients with disease-causing nonsense mutations or an illness linked to dysregulated nonsense transcripts. On the other hand, hundreds of disorders are affected by cellular NMD efficiency and may benefit from NMD-modulatory drugs. Here, we profiled individual FDA-approved drugs for their impact on cellular NMD efficiency using a sensitive method that directly probes multiple endogenous NMD targets for a robust readout of NMD modulation. We found most FDA-approved drugs cause unremarkable effects on NMD, while many elicit clear transcriptional responses. Besides several potential mild NMD modulators, the anticancer drug homoharringtonine (HHT or omacetaxine mepesuccinate) consistently upregulates various endogenous NMD substrates in a dose-dependent manner in multiple cell types. We further showed translation inhibition mediates HHT's NMD effect. In summary, many FDA drugs induce transcriptional changes, and a few impact global NMD, and direct measurement of endogenous NMD substrate expression is robust to monitor cellular NMD.

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