Stress-induced mutagenesis and complex adaptation

Because mutations are mostly deleterious, mutation rates should be reduced by natural selection. However, mutations also provide the raw material for adaptation. Therefore, evolutionary theory suggests that the mutation rate must balance between adaptability—the ability to adapt—and adaptedness—the ability to remain adapted. We model an asexual population crossing a fitness valley and analyse the rate of complex adaptation with and without stress-induced mutagenesis (SIM)—the increase of mutation rates in response to stress or maladaptation. We show that SIM increases the rate of complex adaptation without reducing the population mean fitness, thus breaking the evolutionary trade-off between adaptability and adaptedness. Our theoretical results support the hypothesis that SIM promotes adaptation and provide quantitative predictions of the rate of complex adaptation with different mutational strategies.     

Impaired discrimination of and aversion to parasitized male odors by female oxytocin knockout mice

A major cost of social behavior is the increased risk of exposure to parasites, with animals utilizing social information to recognize and avoid infected conspecifics. In mice, females can discriminate between infected and uninfected males on the basis of social cues, displaying aversive responses to the odors of infected males. In the present study, using female mice whose gene for oxytocin (OT) has been selectively deleted (OT knockout mice (OTKO)), we show that at least one normal allele for OT is required for the mediation of the recognition and avoidance of parasitized males. Female wild type (OTWT) and heterozygous (OTHZ) mice distinguished between the odors of individual males infected with the louse, Polyplax serrata , and uninfected males while the KO mice did not. Exposure to the odors of infected males induced analgesia in OTWT and OTHZ females, with OTKO females displaying attenuated analgesia. OTWT and OTHZ females, but not the OTKO females, also distinguished between the odors of novel and familiar infected males and modulated their analgesic responses on the basis of prior familiarity. In an odor choice test, OTWT and OTHZ females displayed a marked initial choice for the odors of uninfected males, whereas the OTKO females showed no consistent choice. This impairment was specific to the odors of infected males. OTKO females displayed normal analgesic responses to another aversive social odor, that of a stressed male, and an aversive non-social odor, that of a cat. The OTKOs had normal non-social olfactory memory, but were impaired in their social odor memory. These findings indicate that a normal OT gene comprises an essential part of the central recognition mechanism whereby females can both reduce the transmission of parasites to themselves and select for parasite-free males.     

动态心电图对睡眠呼吸暂停综合征的诊断价值及与心律失常的关系分析

目的:评估动态心电图对睡眠呼吸暂停综合征(SAS)的诊断价值并分析其与心律失常的关系。方法:选取2017年2月～2019年2月我院收治的SAS患者80例记为病变组,另取同期于我院进行体检的健康人员80例记为对照组。两组均进行动态心电图检查,并以多导睡眠监测仪检查结果为金标准,分析动态心电图诊断SAS的灵敏度、特异度以及准确度。比较两组动态心电图监测结果,心律失常以及ST-T缺血性改变发生情况。结果:动态心电图诊断SAS的灵敏度、特异度、准确度分别为92.31%、75.00%、90.00%。病变组最高心率、房性早搏次数、室性早搏次数均高于对照组,而最低心率低于对照组(均P0.05)。病变组心律失常及ST-T缺血性改变发生率均高于对照组(均P0.05)。结论:动态心电图对SAS的诊断价值较高,具有良好的灵敏度、特异度。临床工作中可通过动态心电图监测,从而及时检出心律失常及ST-T缺血性改变,进一步有效预防猝死的发生。     

Reduction of exportin 6 activity leads to actin accumulation via failure of RanGTP restoration and NTF2 sequestration in the nuclei of senescent cells

We have previously reported that G-actin accumulation in nuclei is a universal phenomenon of cellular senescence. By employing primary culture of human diploid fibroblast (HDF) and stress-induced premature senescence (SIPS), we explored whether the failure of actin export to cytoplasm is responsible for actin accumulation in nuclei of senescent cells. Expression of exportin 6 (Exp6) and small G-protein, Ran, was significantly reduced in the replicative senescence, but not yet in SIPS, whereas nuclear import of actin by cofilin was already increased in SIPS. After treatment of young HDF cells with H₂O₂, rapid reduction of nuclear RanGTP was observed along with cytoplasmic increase of RanGDP. Furthermore, significantly reduced interaction of Exp6 with RanGTP was found by GST-Exp6 pull-down analysis. Failure of RanGTP restoration was accompanied with inhibition of ATP synthesis and NTF2 sequestration in the nuclei along with accordant change of senescence morphology. Indeed, knockdown of Exp6 expression significantly increased actin molecule in the nuclei of young HDF cells. Therefore, actin accumulation in nuclei of senescent cells is most likely due to the failure of RanGTP restoration with ATP deficiency and NTF2 accumulation in nuclei, which result in the decrease of actin export via Exp6 inactivation, in addition to actin import by cofilin activation.     

Identification of p38MAPK-dependent genes with changed transcript abundance in H2O2-induced premature senescence of IMR-90 hTERT human fibroblasts

Premature senescence of IMR-90 human diploid fibroblasts expressing telomerase (hTERT) establishes after exposure to an acute sublethal concentration of H2O2. We showed herein that p38(MAPK) was phosphorylated after exposure of IMR-90 hTERT cells to H2O2. Selective inhibition of p38(MAPK) activity attenuated the increase in the proportion of cells positive for senescence associated beta-galactosidase activity. We generated a low density DNA array to study gene expression profiles of 240 senescence-related genes. Using this array, p38(MAPK) inhibitor and p38(MAPK) small interferent RNA, we identified several p38(MAPK)-target genes differentially expressed in H2O2-stressed IMR-90 hTERT fibroblasts.     

老年人动态心电图心律失常特点及对阵发性 房颤的诊断

目的:分析65岁以上老年人十二导联动态心电图(12-Holter)心律失常的特点及其对阵发性房颤的诊断价值。方法:①采用回顾性分析的方法,随机选择500例65岁以上老年人的动态心电图进行心律失常情况的统计分析,并同时选择500例小于65岁的心电图作为对照;②另选择500例65岁以上老年人的十二导联普通心电图(ECG)作为对照,对比分析12-Holter与ECG两种方法对老年人阵发性房颤的检出率。结果:①65岁以上老年人动态心电图各种心律失常、ST-T改变的发生率高。而在各类心律失常中房性早搏、室性期前收缩、房性心动过速、房颤发生率较高。②动态心电图对于阵发性房颤的检出率显著高于普通十二导联心电图。结论:①老年人动态心电图检查结果异常率高;②与普通心电图比较,动态心电图诊断老年人阵发性房颤有较高的价值。     

Alternating wide complex tachycardia after surgical aortic valve replacement

A 51-year-old male developed recurrent episodes of palpitations and pre-syncope after surgical aortic valve replacement. Electrocardiograms after surgery revealed a wide complex tachycardia with alternating left bundle branch and right bundle branch block morphologies. An electrophysiology study (EPS) demonstrated typical bundle branch reentry ventricular tachycardia (BBRVT) treated successfully with right bundle ablation. We demonstrate the key diagnostic features of BBRVT on EPS, describe the circuit of BBRVT with explanation of the HV pseudointerval, and highlight the association of BBRVT and valve replacement.     

Geranylgeranoic acid,a bioactive and endogenous fatty acid in mammals: a review

Geranylgeranoic acid (GGA) was first reported in 1983 as one of the mevalonic acid metabolites, but its biological significance was not studied for a long time. Our research on the antitumor effects of retinoids led us to GGA, one of the acyclic retinoids that induce cell death in human hepatoma-derived cell lines. We were able to demonstrate the presence of endogenous GGA in various tissues of male rats, including the liver, testis, and cerebrum, by LC-MS/MS. Furthermore, the biosynthesis of GGA from mevalonic acid in mammals including humans was confirmed by isotopomer spectral analysis using ¹³C-labeled mevalonolactone and cultured hepatoma cells, and the involvement of hepatic monoamine oxidase B in the biosynthesis of GGA was also demonstrated. The biological activity of GGA was analyzed from the retinoid (differentiation induction) and nonretinoid (cell death induction) aspects, and in particular, the nonretinoid mechanism by which GGA induces cell death in hepatoma cells was found to involve pyroptosis via ER stress responses initiated by TLR4 signaling. In addition to these effects of GGA, we also describe the in vivo effects of GGA on reproduction. In this review, based mainly on our published papers, we have shown that hepatic monoamine oxidase B is involved in the biosynthesis of GGA and that GGA induces cell death in human hepatoma-derived cell lines by noncanonical pyroptosis, one of the mechanisms of sterile inflammatory cell death.