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Defects in the posttranscriptional modifications of mitochondrial tRNAs have been linked to human diseases, but their pathophysiology remains elusive. In this report, we investigated the molecular mechanism underlying a deafness-associated tRNAIle 4295A>G mutation affecting a highly conserved adenosine at position 37, 3′ adjacent to the tRNA’s anticodon. Primer extension and methylation activity assays revealed that the m.4295A>G mutation introduced a tRNA methyltransferase 5 (TRMT5)-catalyzed m1G37 modification of tRNAIle. Molecular dynamics simulations suggested that the m.4295A>G mutation affected tRNAIle structure and function, supported by increased melting temperature, conformational changes and instability of mutated tRNA. An in vitro processing experiment revealed that the m.4295A>G mutation reduced the 5′ end processing efficiency of tRNAIle precursors, catalyzed by RNase P. We demonstrated that cybrid cell lines carrying the m.4295A>G mutation exhibited significant alterations in aminoacylation and steady-state levels of tRNAIle. The aberrant tRNA metabolism resulted in the impairment of mitochondrial translation, respiratory deficiency, decreasing membrane potentials and ATP production, increasing production of reactive oxygen species and promoting autophagy. These demonstrated the pleiotropic effects of m.4295A>G mutation on tRNAIle and mitochondrial functions. Our findings highlighted the essential role of deficient posttranscriptional modifications in the structure and function of tRNA and their pathogenic consequence of deafness.

The tissue specificity of mitochondrial tRNA mutations remains largely elusive. In this study, we demonstrated the deleterious effects of tRNAThr 15927G>A mutation that contributed to pathogenesis of coronary artery disease. The m.15927G>A mutation abolished the highly conserved base-pairing (28C-42G) of anticodon stem of tRNAThr. Using molecular dynamics simulations, we showed that the m.15927G>A mutation caused unstable tRNAThr structure, supported by decreased melting temperature and slower electrophoretic mobility of mutated tRNA. Using cybrids constructed by transferring mitochondria from a Chinese family carrying the m.15927G>A mutation and a control into mitochondrial DNA (mtDNA)-less human umbilical vein endothelial cells, we demonstrated that the m.15927G>A mutation caused significantly decreased efficiency in aminoacylation and steady-state levels of tRNAThr. The aberrant tRNAThr metabolism yielded variable decreases in mtDNA-encoded polypeptides, respiratory deficiency, diminished membrane potential and increased the production of reactive oxygen species. The m.15927G>A mutation promoted the apoptosis, evidenced by elevated release of cytochrome c into cytosol and increased levels of apoptosis-activated proteins: caspases 3, 7, 9 and PARP. Moreover, the lower wound healing cells and perturbed tube formation were observed in mutant cybrids, indicating altered angiogenesis. Our findings provide new insights into the pathophysiology of coronary artery disease, which is manifested by tRNAThr mutation-induced alterations.

Mammalian mitochondrial tRNA (mt-tRNA) plays a central role in the synthesis of the 13 subunits of the oxidative phosphorylation complex system (OXPHOS). However, many aspects of the context-dependent expression of mt-tRNAs in mammals remain unknown. To investigate the tissue-specific effects of mt-tRNAs, we performed a comprehensive analysis of mitochondrial tRNA expression across five mice tissues (brain, heart, liver, skeletal muscle, and kidney) using Northern blot analysis. Striking differences in the tissue-specific expression of 22 mt-tRNAs were observed, in some cases differing by as much as tenfold from lowest to highest expression levels among these five tissues. Overall, the heart exhibited the highest levels of mt-tRNAs, while the liver displayed markedly lower levels. Variations in the levels of mt-tRNAs showed significant correlations with total mitochondrial DNA (mtDNA) contents in these tissues. However, there were no significant differences observed in the 2-thiouridylation levels of tRNALys, tRNAGlu, and tRNAGln among these tissues. A wide range of aminoacylation levels for 15 mt-tRNAs occurred among these five tissues, with skeletal muscle and kidneys most notably displaying the highest and lowest tRNA aminoacylation levels, respectively. Among these tissues, there was a negative correlation between variations in mt-tRNA aminoacylation levels and corresponding variations in mitochondrial tRNA synthetases (mt-aaRS) expression levels. Furthermore, the variable levels of OXPHOS subunits, as encoded by mtDNA or nuclear genes, may reflect differences in relative functional emphasis for mitochondria in each tissue. Our findings provide new insight into the mechanism of mt-tRNA tissue-specific effects on oxidative phosphorylation.

Shunpo He,1 Zhenzhen Ye,1 Qingwei Yang,2 Jianzhong Lin,2 Xingyu Chen,2 Zhongjie Chen,2 Liangyi Chen2 1The Graduate School of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Neurology, Zhongshan Hospital, Xiamen University, Xiamen, People’s Republic of ChinaCorrespondence: Qingwei Yang; Xingyu ChenDepartment of Neurology, Zhongshan Hospital, Xiamen University, No. 203 of Hubin South Road, Siming District, Xiamen, 361001, People’s Republic of ChinaTel +86 592-2292113Fax +86 592-2590120Email yamgqimgwei@aliyun.com; chemximgyu@163.comBackground and Aim: Transient global amnesia (TGA) was first described by Bender in 1956 and is characterized by sudden, temporary, and anterograde memory loss. This study aimed to explore the possible mechanisms of and lesions responsible for TGA.Methods: Retrospective data were collected from all patients with TGA admitted to Zhongshan Hospital, affiliated with Xiamen University, between October 1, 2011, and October 30, 2018. Information about the TGA condition, previous history, and clinical examination of the TGA and control groups was recorded. Functional magnetic resonance imaging was performed on the patients to explore the possible lesions responsible for TGA.Results: A total of 73 patients with TGA and 73 age- and gender-matched controls were included in the analysis. The differences in the migraine history (9/2, p = 0.038) were statistically significant in both groups, but no statistically significant difference was observed regarding the history of hypertension, diabetes, and other diseases. In addition, seven patients with TGA had lesions located in the hippocampal CA1 region; the dome column and hippocampal CA1 region exist in the same functional loop and play a synergistic role. The average follow-up period in the groups was 36 months. During the follow-up period, no significant differences in cerebral infarction, cerebral hemorrhage, CHD, or TGA attack between the groups were observed.Conclusion: Migraine may be a risk factor of TGA, and cerebral infarction may be one of the pathogeneses. The brain area responsible for TGA may involve a memory loop comprising the hippocampal CA1 region and the fornix column among other parts.Keywords: transient global amnesia, risk factors, magnetic resonance imaging, responsible lesions, prognosis

As the primary productive force, education plays a huge role in the development of modern society. Traditional educational activities mainly focus on the teaching of students’ superficial knowledge and skills, which are no longer able to meet the current society’s demand for talents. At present, it is required to promote the development of in-depth thinking of college students, stimulate their innovation and creativity, and enable students to better contribute to social production. Therefore, it is very important to introduce the concept of deep learning for college students and establish a student-based teaching model. The author mainly uses mobile learning technology to analyze the functional role of mobile learning technology in promoting deep learning activities for college students, and proposes ways to effectively grasp mobile learning technology in future university informatization education activities.

In this paper, we investigate the low-complexity synchronization design for multi-band orthogonal-frequency-division-multiplexing (MB-OFDM) ultra-wideband (UWB) systems. We propose a unified synchronizer design based on auto-correlation-function. The key component in the proposed synchronizer is a parallel signal detector structure in which multiple auto-correlation units are instantiated and their outputs are shared by other functional units in the synchronizer, including time-frequency pattern detection, symbol timing, carrier frequency offset estimation and correction and frame synchronization. We show that, via analysis and simulations, such a design achieves not only a low computation cost which makes it attractive in implementation, but also equal or better performance compared to the cross-correlation based designs.

We consider the scenario of distributed data aggregation in wireless sensor networks, where each sensor can obtain and estimate the information of the whole sensing field through local data exchange and aggregation. The intrinsic trade-off between energy and delay in aggregation operations imposes a crucial question on nodes to decide optimal instants for forwarding their samples. The samples could be composed of the information from their own sensor readings or an aggregation of information with other samples forwarded from neighboring nodes. By considering the randomness of the sample arrival instants and the uncertainty of the availability of the multiaccess communication channel due to the asynchronous nature of information exchange among neighboring nodes, we propose a decision process model to analyze this problem and determine the optimal decision policies at nodes with local information. We show that, once the statistics of the sample arrival and the availability of the channel satisfy certain conditions, there exist optimal control-limit type policies which are easy to implement in practice. In the case that the required conditions are not satisfied, we provide two learning algorithms to solve a finite-state approximation model of the decision problem. Simulations on a practical distributed data aggregation scenario demonstrate the effectiveness of the developed policies, which can also achieve a desired energy-delay tradeoff.

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