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The physiological impact of the aberrant oxidation products on genomic DNA were demonstrated by embryonic lethality or the cancer susceptibility and/or neurological symptoms of animal impaired in the base excision repair (BER); the major pathway to maintain genomic integrity against non-bulky DNA oxidation. However, growing evidence suggests that other DNA repair pathways or factors that are not primarily associated with the classical BER pathway are also actively involved in the mitigation of oxidative assaults on the genomic DNA, according to the corresponding types of DNA oxidation. Among others, factors dedicated to lesion recognition in the nucleotide excision repair (NER) pathway have been shown to play eminent roles in the process of lesion recognition and stimulation of the enzyme activity of some sets of BER factors. Besides, substantial bulky DNA oxidation can be preferentially removed by a canonical NER mechanism; therefore, loss of function in the NER pathway shares common features arising from BER defects, including cancer predisposition and neurological disorders, although NER defects generally are nonlethal. Here we discuss recent achievements for delineating newly arising roles of NER lesion recognition factors to facilitate the BER process, and cooperative works of BER and NER pathways in response to the genotoxic oxidative stress.

The intricate interplay between DNA damage response (DDR) and metabolism unveils a profound insight into the fundamental mechanisms governing the maintenance of genomic integrity [...].The intricate interplay between DNA damage response (DDR) and metabolism unveils a profound insight into the fundamental mechanisms governing the maintenance of genomic integrity [...].

Neuromorphic computing targets the hardware embodiment of neural network, and device implementation of individual neuron and synapse has attracted considerable attention. The emulation of synaptic plasticity has shown promising results after the advent of memristors. However, neuronal intrinsic plasticity, which involves in learning process through interactions with synaptic plasticity, has been rarely demonstrated. Synaptic and intrinsic plasticity occur concomitantly in learning process, suggesting the need of the simultaneous implementation. Here, we report a neurosynaptic device that mimics synaptic and intrinsic plasticity concomitantly in a single cell. Threshold switch and phase change memory are merged in threshold switch-phase change memory device. Neuronal intrinsic plasticity is demonstrated based on bottom threshold switch layer, which resembles the modulation of firing frequency in biological neuron. Synaptic plasticity is also introduced through the nonvolatile switching of top phase change layer. Intrinsic and synaptic plasticity are simultaneously emulated in a single cell to establish the positive feedback between them. A positive feedback learning loop which mimics the retraining process in biological system is implemented in threshold switch-phase change memory array for accelerated training. Synaptic plasticity and neuronal intrinsic plasticity are both involved in the learning process of hardware artificial neural network. Here, Lee et al. integrate a threshold switch and a phase change memory in a single device, which emulates biological synaptic and intrinsic plasticity simultaneously.

Genetic loss or mutations in tumor suppressor genes promote tumorigenesis. The prospective tumor suppressor tristetraprolin (TTP) has been shown to negatively regulate tumorigenesis through destabilizing the messenger RNAs of critical genes implicated in both tumor onset and tumor progression. Regulation of TTP has therefore emerged as an important issue in tumorigenesis. Similar to other tumor suppressors, TTP expression is frequently downregualted in various human cancers, and its low expression is correlated with poor prognosis. Additionally, disruption in the regulation of TTP by various mechanisms results in the inactivation of TTP protein or altered TTP expression. A recent study showing alleviation of Myc-driven lymphomagenesis by the forced expression of TTP has shed light on new therapeutic avenues for cancer prevention and treatment through the restoration of TTP expression. In this review, we summarize key oncogenes subjected to the TTP-mediated mRNA degradation, and discuss how dysregulation of TTP can contribute to tumorigenesis. In addition, the control mechanism underlying TTP expression at the posttranscriptional and posttranslational levels will be discussed.

Transcription-coupled repair (TCR) and R-loops are two interrelated processes critical to the maintenance of genome stability during transcription. TCR, a specialized sub-pathway of nucleotide excision repair, rapidly removes transcription-blocking lesions from the transcribed strand of active genes, thereby safeguarding transcription fidelity and cellular homeostasis. In contrast, R-loops, RNA–DNA hybrid structures formed co-transcriptionally, play not only regulatory roles in gene expression and replication but can also contribute to genome instability when persistently accumulated. Recent experimental evidence has revealed dynamic crosstalk between TCR and R-loop resolution pathways. This review highlights current molecular and cellular insights into TCR and R-loop biology, discusses the impact of their crosstalk, and explores emerging therapeutic strategies aimed at optimizing DNA repair and reducing disease risk in conditions such as cancer and neurodegenerative disorders.

The distance-dependent coseismic and postseismic displacements produced by the 2011 M W 9.0 Tohoku-Oki megathrust earthquake caused medium weakening and stress perturbation in the crust around the Korean Peninsula, increasing the seismicity with successive M L 5-level earthquakes at the outskirts of high seismicity regions. The average M L 5-level occurrence rate prior to the megathrust earthquake was 0.15 yr −1 (0.05–0.35 yr −1 at a 95% confidence level), and the rate has increased to 0.71 yr −1 (0.23–1.67 yr −1 at a 95% confidence level) since the megathrust earthquake. The 2016 M L 5-level midcrustal earthquakes additionally changed the stress field in adjacent regions, inducing the 15 November 2017 M L 5.4 earthquake. The successive 2016 and 2017 moderate-size earthquakes built complex stress fields in the southeastern Korean Peninsula, increasing the seismic hazard risks in the regions of long-term stress accumulation. The increased seismic risks may continue until the medium properties and stress field are recovered.

(Cancer Sci 2010; 101: 579–585) Cholangiocarcinoma is relatively rare, but high incidence rates have been reported in Eastern Asia, especially in Thailand. The etiology of this cancer of the bile ducts appears to be mostly due to specific infectious agents. In 2009, infections with the liver flukes, Clonorchis sinensis or Opistorchis viverrini, were both classified as carcinogenic to humans by the International Agency for Research on Cancer for cholangiocarcinoma. In addition, a possible association between chronic infection with hepatitis B and C viruses and cholangiocarcinoma was also noted. The meta‐analysis of published literature revealed the summary relative risks of infection with liver fluke (both Opistorchis viverrini and Clonorchis sinensis), hepatitis B virus, and hepatitis C virus to be 4.8 (95% confidence interval [95% CI]: 2.8–8.4), 2.6 (95% CI: 1.5–4.6), and 1.8 (95% CI: 1.4–2.4), respectively – liver fluke infection being the strongest risk factor for cholangiocarcinoma. Countries where human liver fluke infection is endemic include China, Korea, Vietnam, Laos, and Cambodia. The number of infected persons with Clonorchis sinensis in China has been estimated at 12.5 million with considerable variations among different regions. A significant regional variation in Opistorchis viverrini prevalence was also noted in Thailand (average 9.6% or 6 million people). The implementation of a more intensive preventive and therapeutic program for liver fluke infection may reduce incidence rates of cholangiocarcinoma in endemic areas. Recently, advances have been made in the diagnosis and management of cholangiocarcinoma. Although progress on cholangiocarcinoma prevention and treatment has been steady, more studies related to classification and risk factors will be helpful to develop an advanced strategy to cure and prevent cholangiocarcinoma.

The development of deep learning has achieved great success in object detection, but small object detection is still a difficult and challenging task in computer vision. To address the problem, we propose an improved single-shot multibox detector (SSD) using enhanced feature map blocks (SSD-EMB). The enhanced feature map block (EMB) consists of attention stream and feature map concatenation stream. The attention stream allows the proposed model to focus on the object regions rather than background owing to channel averaging and the effectiveness of the normalization. The feature map concatenation stream provides additional semantic information to the model without degrading the detection speed. By combining the output of these two streams, the enhanced feature map, which improves the detection of a small object, is generated. Experimental results show that the proposed model has high accuracy in small object detection. The proposed model not only achieves good detection accuracy, but also has a good detection speed. The SSD-EMB achieved a mean average precision (mAP) of 80.4% on the PASCAL VOC 2007 dataset at 30 frames per second on an RTX 2080Ti graphics processing unit, an mAP of 79.9% on the VOC 2012 dataset, and an mAP of 26.6% on the MS COCO dataset.

Genomic integrity is constantly insulted by solar ultraviolet (UV) radiation. Adaptative cellular mechanisms called DNA damage responses comprising DNA repair, cell cycle checkpoint, and apoptosis, are believed to be evolved to limit genomic instability according to the photoperiod during a day. As seen in many other key cellular metabolisms, genome surveillance mechanisms against genotoxic UV radiation are under the control of circadian clock systems, thereby exhibiting daily oscillations in their catalytic activities. Indeed, it has been demonstrated that nucleotide excision repair (NER), the sole DNA repair mechanism correcting UV-induced DNA photolesions, and ataxia–telangiectasia-mutated and Rad3-related (ATR)-mediated cell cycle checkpoint kinase are subjected to the robust control of the circadian clock. The molecular foundation for the circadian rhythm of UV-induced DNA damage responses in mammalian cells will be discussed.

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic emaciating disease of ruminants that causes enormous economic losses to the bovine industry, globally. However, there are still remaining clues to be solved in the pathogenesis and diagnosis of the disease. Therefore, an in vivo murine experimental model was tried to understand responses in early stage of MAP infection by oral and intraperitoneal (IP) routes. In the MAP infection size, and weight of spleen and liver were increased in the IP group compared with oral groups. Severe histopathological changes were also observed in the spleen and liver of IP infected mice at 12 weeks post-infection (PI). Acid-fast bacterial burden in the organs was closely related to histopathological lesions. In the cytokine production from splenocytes of MAP-infected mice, higher amounts of in TNF-α, IL-10, and IFN-γ were produced at early stage of IP-infected mice while IL-17 production was different at time and infected groups. This phenomenon may indicate the immune shift from Th1 to Th17 through the time course of MAP infection. Systemic and local responses in the MAP-infection were analyzed by using transcriptomic analysis in the spleens and mesenteric lymph nodes (MLN). Based on the analysis of biological processes at 6 weeks PI in spleen and MLN in each infection group, canonical pathways were analyzed with ingenuity pathway analysis in the immune responses and metabolism especially lipid metabolism. Infected host cells with MAP increased in the production of proinflammatory cytokines and reduced the availability of glucose at early stage of infection ( p < 0.05). Also, host cells secreted cholesterol through cholesterol efflux to disturb energy source of MAP. These results reveal immunopathological and metabolic responses in the early stage of MAP infection through the development of a murine model.