Combining proteomics and lipid analysis to unravel Confidor stress response in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is a useful model for studying the influence of different stress factors on eukaryotic cells. In this work we used the pesticide imidacloprid, in the Confidor formulation, as the stress factor and analyzed its influence on the metabolic activity, proteome and lipid content and composition of Saccharomyces cerevisiae yeast. During the cultivation of yeast, the lowest recommended application dose of Confidor (0.025%, v/v) was added to the growth media and its influence on the mitochondria, cytosol with microsomes, and the whole yeast cells was monitored. The results show that under the stress provoked by the toxic effects of Confidor, yeast cells density significantly decreased and the percentage of metabolically disturbed cells significantly increased comparing with untreated control. Also, there was a downregulation of majority of glycolytic, gluconeogenesis, and TCA cycle enzymes (Fba1, Adh1, Hxk2, Tal1, Tdh1,Tdh3, Eno1) thus providing enough acetyl‐CoA for the lipid restructuring and accumulation mechanism since we have found the changes in the cell and mitochondrial lipid content and FA composition. This data suggest that lipids could be the molecules that orchestrate the answer of the cells in the stress response to the Confidor treatment.     

How important is embeddedness in predicting Australian speech–language pathologists’ intentions to leave their jobs and the profession?

Purpose: This study explored the predictors of the outcomes of turnover and occupation attrition intentions for speech-language pathologists. The researchers examined the mediating effects of job satisfaction and strain on the relationship between stress and the latter outcomes. Additionally, the researchers examined the importance of embeddedness in predicting turnover intentions after accounting for stress, strain and job satisfaction.

Method: An online questionnaire was used to explore turnover and attrition intentions in 293 Australian speech–language pathologists.

Result: Job satisfaction contributed to a significant indirect effect on the stress and turnover intention relationship, however strain did not. There was a significant direct effect between stress and turnover intention after accounting for covariates. Embeddedness and the perceived availability of alternative jobs were also found to be significant predictors of turnover intentions. The mediating model used to predict turnover intentions also predicted occupation attrition intentions. The effect of stress on occupation attrition intentions was indirect in nature, the direct effect negated by mediating variables. Qualitative data provided complementary evidence to the quantitative model.

Conclusion: The findings indicate that the proposed parsimonious model adequately captures predictors of speech–language pathologists’ turnover and occupation attrition intentions. Workplaces and the profession may wish to consider these retention factors.     

黄芪多糖对毒胡萝卜素诱导人结肠癌系HT29细胞内质网应激的影响

目的探讨黄芪多糖(Astragalus polysaccharides,AP)对毒胡萝卜素内酯(Thapsigargin,Tg)诱导人结肠癌系HT29细胞发生内质网应激(Endoplasmic Reticulum Stress,ERS)时内质网结构变化及相关分子GRP78和CHOP的影响。方法常规培养HT29细胞后,将细胞分为4组:①空白细胞组(Control组):细胞不做任何药物处理;②细胞模型组(Model组):采用1μmol/L Tg诱导HT29细胞建立ERS模型;③黄芪多糖低浓度组(AP-L组);④黄芪多糖高浓度组(AP-H组)。CCK8法检测黄芪多糖对HT29细胞活性,透射电镜观察内质网结构变化,Real-time PCR法检测ERS时GRP78、CHOP mRNA表达情况。结果黄芪多糖浓度分别为1、10μg/mL,且分别作用HT29细胞12、24、36、48 h时,细胞存活率随着浓度的增加而增加,说明对细胞无明显毒副作用。透射电镜观察Control组内质网结构呈网膜状结构,网膜腔不扩张;Model组内质网形态迥异,大小不一,呈空泡状改变,部分可见融合成簇现象;AP-L组内质网网膜腔扩张程度减轻,空泡体积减小和数量减少;AP-H组内质网形态基本恢复正常,呈网膜状结构,可见数量较少,形态较小的空泡状结构。Real-time PCR法检测结果:与Control组相比,Model组HT29细胞GRP78、CHOP mRNA表达明显增加(P<0.05);与Model组比较,AP-L组和AP-H组HT29细胞GRP78、CHOP mRNA表达均减少(P<0.05);与AP-L组比较,AP-H组HT29细胞GRP78、CHOP mRNA表达减少(P<0.05)。结论黄芪多糖能够抑制Tg诱导HT29细胞发生ERS,其机制可能与降低GRP78和CHOP的表达、减轻内质网应激有关。     

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.     

人格特征对男性喉鳞状细胞癌患者术后近期心理状况的影响

目的 探讨人格特征对喉鳞状细胞癌（LSCC）患者术后近期心理健康状况的影响。方法 纳入2017年1月—2019年12月在湖北省肿瘤医院行手术治疗的119例男性LSCC患者，术后5~7 d采用SCL-90、SAS、SDS自评量表评估术后心理状态，采用EPQ问卷测评患者的人格特征。多元线性逐步回归方法分析LSCC患者术后近期SAS和SDS评分的影响因素。结果 男性LSCC患者术后SCL-90、SAS、SDS得分显著高于中国常模（P≤0.05），EPQ中精神质（P）量表和神经质（N）量表得分高于中国常模（P<0.01）。男性LSCC患者术后躯体化、强迫、焦虑、抑郁、敌对、恐怖、偏执、精神病性因子得分均显著高于中国常模（P<0.05）。家庭收入、手术方式、术后近期是否行放化疗、P和N人格特征是术后SAS评分的影响因素（均P<0.01）；家庭收入、手术方式、术后近期是否行放化疗和N人格特征是术后SDS评分的影响因素（P<0.01）。结论 LSCC患者术后近期存在抑郁、焦虑等心理障碍；具有P和N人格特征；家庭收入、手术方式、术后近期是否行放化疗以及P和N人格特征是影响术后SAS及SDS评分的独立危险因素。     

Do different types of stress differentially alter behavioural and neurobiological outcomes associated with depression in rodent models? A systematic review

Cataloguing the effects of different types of stress on behaviour and physiology in rodent models has not been comprehensively attempted. Here, we systematically review whether chronic exposure to physical stress, psychosocial stress, or both types of stress can induce different behavioural and neurobiological outcomes in male and female rodents. We found that physical stress consistently increased depressive-like behaviour, impaired social interaction and decreased body weight, while psychosocial stress consistently increased both anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity, peripheral inflammation and microglial activation, and decreased hippocampal neurogenesis in male rodents. Moreover, we found that the combined effect of both stress types resulted in a more severe pathological state defined by increased anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity and central inflammation, and reduced hippocampal neurogenesis and neural plasticity in male rodents. Phenotypes for females were less consistent, irrespective of the type of stress exposure, on account of the limited number of studies using females. This review highlights that the type of stress may indeed matter and will help animal researchers to more appropriately choose a stress/depression model that fits their research purposes.