ZmbZIP60 mRNA is spliced in maize in response to ER stress

<p>Abstract</p> <p>Background</p> <p>Adverse environmental conditions produce ER stress and elicit the unfolded protein response (UPR) in plants. Plants are reported to have two "arms" of the ER stress signaling pathway-one arm involving membrane-bound transcription factors and the other involving a membrane-associated RNA splicing factor, IRE1. IRE1 in yeast to mammals recognizes a conserved twin loop structure in the target RNA.</p> <p>Results</p> <p>A segment of the mRNA encoding ZmbZIP60 in maize can be folded into a twin loop structure, and in response to ER stress this mRNA is spliced, excising a 20b intron. Splicing converts the predicted protein from a membrane-associated transcription factor to one that is targeted to the nucleus. Splicing of ZmbZIP60 can be elicited in maize seedlings by ER stress agents such as dithiothreitol (DTT) or tunicamycin (TM) or by heat treatment. Younger, rather than older seedlings display a more robust splicing response as do younger parts of leaf, along a developmental gradient in a leaf. The molecular signature of an ER stress response in plants includes the upregulation of Binding Protein (BIP) genes. Maize has numerous BIP-like genes, and ER stress was found to upregulate one of these, ZmBIPb.</p> <p>Conclusions</p> <p>The splicing of ZmbZIP60 mRNA is an indicator of ER stress in maize seedlings resulting from adverse environmental conditions such as heat stress. ZmbZIP60 mRNA splicing in maize leads predictively to the formation of active bZIP transcription factor targeted to the nucleus to upregulate stress response genes. Among the genes upregulated by ER stress in maize is one of 22 BIP-like genes, ZmBIPb.</p

Acceptability, feasibility, and user satisfaction of a virtual reality relaxation intervention in a psychiatric outpatient setting during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic was particularly difficult for individuals with mental disorders. Due to governmental restrictions, face-to-face offers for psychiatric outpatients like therapies, psychoeducational groups or relaxation courses were limited. Virtual reality (VR) might be a new possibility to support these patients by providing them with a home-based relaxation tool.ObjectiveThe aim of this study was to evaluate the acceptability, feasibility, and user satisfaction of a supportive therapy-accompanying, relaxation VR intervention in psychiatric outpatients during the COVID-19 pandemic in Germany.MethodsThe four-weeks VR intervention consisted of regular watching of relaxing videos in the participants’ home environment. Sociodemographics, feasibility (frequency of use, user-friendliness), satisfaction (Client Satisfaction Questionnaire-8), depressive symptoms (Patient Health Questionnaire-9), quality of life (abbreviated World Health Organization Quality of Life assessment), and credibility and expectancy (Credibility Expectancy Questionnaire-8) were measured in an intention-to-treat (ITT) analysis and a per-protocol (PP) analysis of completers.ResultsIn total, N = 40 patients participated in the study. Most of the participants in the ITT analysis (n = 30, 75.0%) used the VR device three or 4 weeks. A majority of the N = 29 completers (PP: n = 18, 62.1%) used it all 4 weeks. Most participants used the device two or more times a week (ITT: n = 30, 83.3%; PP: n = 26, 89.7%) and described the user-friendliness as rather or very easy (ITT: n = 33, 91.7%; PP: n = 26, 89.7%). User satisfaction was high (ITT: 19.42, SD = 4.08; PP: M = 20.00, SD = 4.19) and did not correlate with participants’ sex or age (all p &lt; 0.05). Depressive symptoms and psychological quality of life improved significantly from pre-to post-intervention (ITT and PP, all p &lt; 0.05). Higher pre-intervention credibility significantly correlated with a better outcome of satisfaction (ITT and PP), depressive symptoms, physical, psychological, and social quality of life (PP; all p &lt; 0.05).ConclusionA supportive therapy-accompanying VR relaxation intervention is feasible and acceptable in a psychiatric outpatient setting. Due to the high satisfaction and user-friendliness, VR can be an easy to implement relaxation tool to support psychiatric outpatients.Clinical trial registrationhttps://clinicaltrials.gov/, DRKS00027911

Role for miR-204 in human pulmonary arterial hypertension

Reduced miR-204 expression facilitates the excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells characteristic of human pulmonary arterial hypertension

Alteration of the bZIP60/IRE1 Pathway Affects Plant Response to ER Stress in Arabidopsis thaliana

The Unfolded Protein Response (UPR) is elicited under cellular and environmental stress conditions that disrupt protein folding in the endoplasmic reticulum (ER). Through the transcriptional induction of genes encoding ER resident chaperones and proteins involved in folding, the pathway contributes to alleviating ER stress by increasing the folding capacity in the ER. Similarly to other eukaryotic systems, one arm of the UPR in Arabidopsis is set off by a non-conventional splicing event mediated by ribonuclease kinase IRE1b. The enzyme specifically targets mature bZIP60 RNA for cleavage, which results in a novel splice variant encoding a nuclear localized transcription factor. Although it is clear that this molecular switch widely affects the transcriptome, its exact role in overall plant response to stress has not been established and mutant approaches have not provided much insight. In this study, we took a transgenic approach to manipulate the pathway in positive and negative fashions. Our data show that the ER-resident chaperone BiP accumulates differentially depending on the level of activation of the pathway. In addition, phenotypes of the transgenic lines suggest that BiP accumulation is positively correlated with plant tolerance to chronic ER stress

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Les jeux de harsard et d'argent (quand le loisir devient une addiction)

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Distinct domains within the NITROGEN LIMITATION ADAPTATION protein mediate its subcellular localization and function in the nitrate-dependent phosphate homeostasis pathway

The NITROGEN LIMITATION ADAPTATION (NLA) protein is a RING-type E3 ubiquitin ligase that plays an essential role in the regulation of nitrogen and phosphate homeostasis. NLA is localized to two different subcellular sites, the plasma membrane and nucleus, and contains four distinct domains: i) a RING domain that mediates degradation of phosphate transporters at the plasma membrane; ii) an SPX domain that facilitates NLAâ s interaction with the phosphate transporters, and also exists in other proteins that regulate the nuclear transcription factors that control the phosphate starvation response pathway; iii) a linker domain that lies between the RING and SPX domains; and iv) a C-terminal domain, which, like the linker region, is of unknown function. Here we carried out a mutational analysis of NLA, which indicated that all the domains are not only essential for proper functioning of the protein, but also mediate its localization to the plasma membrane and/or nucleus, as well as to different subdomains within the nucleus. Overall, the results provide new insights to the distinct protein motifs within NLA and the role(s) that this protein serves at different subcellular sites with respect to the regulation of nitrogen-dependent phosphate homeostasis as well as other possible physiological functions.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author