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Milena Jankovic Ivana Novakovic Dejan Nikolic Jasmina Mitrovic Maksic Slavko Brankovic Ivana Petronic Dragana Cirovic Sinisa Ducic Mirko Grajic Dragana Bogicevic 《International journal of molecular sciences》2021,22(9)
Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN. 相似文献
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Franois Ancien Fabrizio Pucci Marianne Rooman 《International journal of molecular sciences》2021,22(9)
Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality. 相似文献
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Understanding the mechanisms leading to the rise and dissemination of antimicrobial resistance (AMR) is crucially important for the preservation of power of antimicrobials and controlling infectious diseases. Measures to monitor and detect AMR, however, have been significantly delayed and introduced much later after the beginning of industrial production and consumption of antimicrobials. However, monitoring and detection of AMR is largely focused on bacterial pathogens, thus missing multiple key events which take place before the emergence and spread of AMR among the pathogens. In this regard, careful analysis of AMR development towards recently introduced antimicrobials may serve as a valuable example for the better understanding of mechanisms driving AMR evolution. Here, the example of evolution of tet(X), which confers resistance to the next-generation tetracyclines, is summarised and discussed. Initial mechanisms of resistance to these antimicrobials among pathogens were mostly via chromosomal mutations leading to the overexpression of efflux pumps. High-level resistance was achieved only after the acquisition of flavin-dependent monooxygenase-encoding genes from the environmental microbiota. These genes confer resistance to all tetracyclines, including the next-generation tetracyclines, and thus were termed tet(X). ISCR2 and IS26, as well as a variety of conjugative and mobilizable plasmids of different incompatibility groups, played an essential role in the acquisition of tet(X) genes from natural reservoirs and in further dissemination among bacterial commensals and pathogens. This process, which took place within the last decade, demonstrates how rapidly AMR evolution may progress, taking away some drugs of last resort from our arsenal. 相似文献
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基于GA-BP的汽车风振噪声声品质预测模型 总被引:1,自引:1,他引:0
目前对于汽车风振噪声的优化研究主要以声压级(Sound pressure level,SPL)作为单一评价指标,既不能全面反映噪声的物理属性,也无法考虑人耳对噪声的主观认知过程。为准确评价风振噪声,引入声品质,运用大涡模拟(Large eddy simulation,LES)对风振噪声进行数值仿真,根据实车道路试验判断仿真的准确性;对仿真结果进行声品质客观评价与主观评价,综合声品质客观评价参数与声品质主观评价试验结果建立BP神经网络预测模型;利用遗传算法(Genetic algorithm,GA),进一步对BP神经网络的结构参数进行优化,建立GA-BP声品质预测模型。研究结果表明,GA-BP声品质预测模型在训练速度和预测精度上都优于BP神经网络预测模型。预测模型基于声品质主客观评价结果,其预测值可以代替传统的声压级评价指标,为风振噪声提供更为准确合理的评价。 相似文献
6.
Under the circumstance of perceptual consumption, it is still challenging to grasp consumer's emotions and demands due to the large search space, diversified preferences, and easy fatigue of consumers. To reduce user fatigue and enlarge search space, a novel method was presented to design and optimize the pattern of yarn-dyed plaid fabric using the isolation niche genetic algorithm and rough set theory. Each pattern was encoded as a chromosome based on the real number code. The population was initialized and evolved using INGA to maintain the diversity. The rough set theory was adopted as the fitness function of isolation niche genetic algorithm to extract the consumer's demands. After multiple evolutions, a large set of practical patterns of the yarn-dyed plaid fabric are obtained. Experiments were carried out by 24 testers of different ages and genders. The results prove that the proposed method based on the isolation niche genetic algorithm and rough set theory is feasible and effective, supplying references to the designer. 相似文献
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Quinoline is widely used in the production of drugs as a highly effective insecticide, and its derivatives can also be used to produce dyes. It has a teratogenic carcinogen to wildlife and humans once entering into the aquatic environment. In this study, the degradation mechanism of quinoline in drinking water by a strong ionization dielectric barrier discharge(DBD) lowtemperature plasma with large volume was explored. High concentration of hydroxyl radical(·OH)(0.74 mmol l-1) and ozone(O3)(58.2 mg l-1) produced by strongly ionized discharge DBD system were quantitatively analyzed based on the results of electron spin resonance and O3 measurements. The influencing reaction conditions of input voltages, initial p H value, ·OH inhibitors, initial concentration and inorganic ions on the removal efficiency of quinoline were systematically studied. The obtained results showed that the removal efficiency and TOC removal of quinoline achieved 94.8% and 32.2%, degradation kinetic constant was 0.050 min-1 at 3.8 k V and in a neutral p H(7.2). The proposed pathways of quinoline were suggested based on identified intermediates as hydroxy pyridine, fumaric acid, oxalic acid, and other small molecular acids by high-performance liquid chromatography/tandem mass spectrometry analysis. Moreover, the toxicity analysis on the intermediates demonstrated that its acute toxicity, bioaccumulation factor and mutagenicity were reduced. The overall findings provided theoretical and experimental basis for the application of a high capacity strong ionization DBD water treatment system in the removal of quinoline from drinking water. 相似文献
9.
The scarcity of industrial and domestic use water has become an important issue as industrial operations and localized pollution have burgeoned over the last decade. Wastewater (WW) treatment for recycling and reuse is gaining importance as an alternate source of water supply to circumvent water shortages. Wastewater treatment requires thorough planning, design, construction, and management of treatment facilities in order to discharge the treated water to the aquatic environment or for recycling and reuse. One detrimental effect of growing populations and urbanization has been the release of many persistent emerging contaminants (ECs) to the environment, mainly detected in WW. The entry of these ECs to the aquatic environment through wastewater treatment plants (WWTPs) may cause different ecological risks such as reproductive toxicity, endocrine disruption, and microbial resistance. The quantification of ECs (in ng or pg level) in complex matrices, such as WW samples recognized through non‐target screening approaches, has played a key role in the planning and design of water treatment facilities. The purpose of this review is to provide information about advancements in wastewater treatment technologies such as constructed wetland (CW) and advanced oxidation processes (AOPs) and the fate of emerging contaminants during these treatments. Further, this review also reports the ecological effects of these contaminants and their by‐products formed during various advanced WW treatment processes. The review also discusses advancements in different analytical techniques for the analysis of ECs in WW. 相似文献
10.
通过对3-UPS并联机器人进行动力学建模与状态空间分析,基于遗传算法(GA)优化的线性二次型调节器(LQR)控制方法对其进行控制仿真,结合多体系统振动理论,并运用MATLAB软件和ADAMS软件联合仿真,分别对该并联机器人在动平台施加外部载荷、定平台施加随机振动,以及动、定平台施加复合干扰3种情况下机器人的末端稳定性进行分析。结果表明:GA优化的LQR控制下,机器人动平台质心振动的衰减时间和振动幅度都明显减小,且共振峰也明显降低,但是高频振动处的减振效果不明显;机器人动平台质心x和y方向的共振频率均保持在5 Hz左右,而z方向的共振频率却有明显的后移现象,逐渐向高频(10 Hz)靠近。该研究为分析并联机器人稳定性与工作精度提供了一定的理论基础。 相似文献