scholarly journals Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Inah Hwang ◽  
Hiroki Uchida ◽  
Ziwei Dai ◽  
Fei Li ◽  
Teresa Sanchez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Environmental Changes ◽  
Type I ◽  
Neurogenic Differentiation ◽  
Forkhead Box ◽  
Nuclear Lamin ◽  
Neural Stem Progenitor Cells ◽  
Subsequent Activation ◽  
Methyl Group Transfer

AbstractNeural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes like elevated oxidative stress. But how oxidative stress regulates NSPC and its neurogenic differentiation is less clear. Here we report that acutely elevated cellular oxidative stress in NSPCs modulates neurogenic differentiation through induction of Forkhead box protein O3 (FOXO3)-mediated cGAS/STING and type I interferon (IFN-I) responses. We show that oxidative stress activates FOXO3 and its transcriptional target glycine-N-methyltransferase (GNMT) whose upregulation triggers depletion of s-adenosylmethionine (SAM), a key co-substrate involved in methyl group transfer reactions. Mechanistically, we demonstrate that reduced intracellular SAM availability disrupts carboxymethylation and maturation of nuclear lamin, which induce cytosolic release of chromatin fragments and subsequent activation of the cGAS/STING-IFN-I cascade to suppress neurogenic differentiation. Together, our findings suggest the FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signaling cascade as a critical stress response program that regulates long-term regenerative potential.

scholarly journals Cellular Stress Signaling Activates Type-I IFN Response Through FOXO3-regulated Lamin Posttranslational Modification

2020 ◽  
Author(s):  
Inah Hwang ◽  
Ziwei Dai ◽  
Fei Li ◽  
Teresa Sanchez ◽  
Jason W Locasale ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Environmental Changes ◽  
Dynamic Balance ◽  
Type I ◽  
Nuclear Lamin ◽  
Neural Stem Progenitor Cells ◽  
Subsequent Activation ◽  
Methyl Group Transfer

AbstractNeural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes, including elevated oxidative stress. A time-dependent stress response that regulates the dynamic balance between quiescence and differentiation is thus essential to preserve NSPC long-term regenerative potential. Here we report that acutely elevated cellular oxidative stress in NSPCs suppresses neurogenic differentiation through induction of FOXO3-mediated cGAS/STING and type I interferon (IFN-I) responses. We show that oxidative stress activates FOXO3 promoting upregulation of its transcriptional target glycine-N-methyltransferase (GNMT) and thus depletion of s-adenosylmethionine (SAM), a key co-substrate involved in methyl group transfer reactions. Mechanistically, we demonstrate that reduced intracellular SAM availability disrupts carboxymethylation and maturation of nuclear lamin, which trigger cytosolic release of chromatin fragments and subsequent activation of the cGAS/STING/IFN-I cascade. Together, our findings suggest the FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signaling cascade as a critical stress response program that preserves its long-term regenerative potential.

scholarly journals Effects of long-term ethanol administration in a rat total enteral nutrition model of alcoholic liver disease

2011 ◽  
Vol 300 (1) ◽  
pp. G109-G119 ◽  
Author(s):  
Martin J. J. Ronis ◽  
Leah Hennings ◽  
Ben Stewart ◽  
Alexei G. Basnakian ◽  
Eugene O. Apostolov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Enteral Nutrition ◽  
Hepatic Steatosis ◽  
Hepatocyte Proliferation ◽  
Ethanol Administration ◽  
Fatty Acid Transport ◽  
Type I ◽  
Total Enteral Nutrition

Male Sprague-Dawley rats were chronically fed a high-unsaturated-fat diet for 130 days by using total enteral nutrition (TEN), or the same diet in which ethanol (EtOH) isocalorically replaced carbohydrate calories. Additional groups were supplemented with the antioxidant N-acetylcysteine (NAC) at 1.7 g·kg−1·day−1. Relative to an ad libitum chow-fed group, the high-fat-fed controls had three- to fourfold greater expression of fatty acid transporter CD36 mRNA and developed mild steatosis but little other hepatic pathology. NAC treatment resulted in increased somatic growth relative to controls (4.0 ± 0.1 vs. 3.1 ± 0.1 g/day) and increased hepatic steatosis score (3.5 ± 0.6 vs. 2.7 ± 1.2), associated with suppression of the triglyceride hydrolyzing protein adiponutrin, but produced no elevation in serum alanine aminotransferase (ALT). Chronic EtOH treatment increased expression of fatty acid transport protein FATP-2 mRNA twofold, resulting in marked hepatic steatosis, oxidative stress, and a twofold elevation in serum ALT. However, no changes in tumor necrosis factor-α or transforming growth factor-β expression were observed. Fibrosis, as measured by Masson's trichrome and picrosirius red staining, and a twofold increase in expression of type I and type III collagen mRNA, was only observed after EtOH treatment. Long-term EtOH treatment increased hepatocyte proliferation but did not modify the hepatic mRNAs for hedgehog pathway ligands or target genes or genes regulating epithelial-to-mesenchymal transition. Although the effects of NAC on EtOH-induced fibrosis could not be fully evaluated, NAC had additive effects on hepatocyte proliferation and prevented EtOH-induced oxidative stress and necrosis, despite a failure to reverse hepatic steatosis.

Comparative Study of effectiveness of mobilization with movement (MWM) and End range mobilization (ERM) techniques in frozen shoulder

2018 ◽  
Vol 4 (4) ◽  
pp. 519-522
Author(s):  
Jeyakumar S ◽  
Jagatheesan Alagesan ◽  
T.S. Muthukumar
Keyword(s):  
Range Of Motion ◽  
Frozen Shoulder ◽  
Type I ◽  
Mean Values ◽  
Functional Activities ◽  
Group A ◽  
The Mean ◽  
Group B

Background: Frozen shoulder is disorder of the connective tissue that limits the normal Range of motion of the shoulder in diabetes, frozen shoulder is thought to be caused by changes to the collagen in the shoulder joint as a result of long term Hypoglycemia. Mobilization is a therapeutic movement of the joint. The goal is to restore normal joint motion and rhythm. The use of mobilization with movement for peripheral joints was developed by mulligan. This technique combines a sustained application of manual technique “gliding” force to the joint with concurrent physiologic motion of joint, either actively or passively. This study aims to find out the effects of mobilization with movement and end range mobilization in frozen shoulder in Type I diabetics. Materials and Methods: 30 subjects both male and female, suffering with shoulder pain and clinically diagnosed with frozen shoulder was recruited for the study and divided into two groups with 15 patients each based on convenient sampling method. Group A patients received mobilization with movement and Group B patients received end range mobilization for three weeks. The outcome measurements were SPADI, Functional hand to back scale, abduction range of motion using goniometer and VAS. Results: The mean values of all parameters showed significant differences in group A as compared to group B in terms of decreased pain, increased abduction range and other outcome measures. Conclusion: Based on the results it has been concluded that treating the type 1 diabetic patient with frozen shoulder, mobilization with movement exercise shows better results than end range mobilization in reducing pain and increase functional activities and mobility in frozen shoulder.

Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus

Diabetes ◽  
1984 ◽  
Vol 33 (4) ◽  
pp. 394-400 ◽  
Author(s):  
G. Bolli ◽  
P. De Feo ◽  
S. De Cosmo ◽  
G. Perriello ◽  
G. Angeletti ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Type I Diabetes ◽  
Type I Diabetes Mellitus ◽  
Type I ◽  
Short Term

Designing a CRM Framework for online & offline sports footwear retailers

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Rodrigo Cueva ◽  
Guillem Rufian ◽  
Maria Gabriela Valdes
Keyword(s):  
Environmental Changes ◽  
Customer Relationship ◽  
Business Strategies ◽  
Economic Sectors ◽  
Running Shoes ◽  
Brick And Mortar ◽  
Key Factor ◽  
On Line ◽  
The Impact

The use of Customer Relationship Managers to foster customers loyalty has become one of the most common business strategies in the past years.  However, CRM solutions do not fill the abundance of happily ever-after relationships that business needs, and each client’s perception is different in the buying process.  Therefore, the experience must be precise, in order to extend the loyalty period of a customer as much as possible. One of the economic sectors in which CRM’s have improved this experience is retailing, where the personalized attention to the customer is a key factor.  However, brick and mortar experiences are not enough to be aware in how environmental changes could affect the industry trends in the long term.  A base unified theoretical framework must be taken into consideration, in order to develop an adaptable model for constructing or implementing CRMs into companies. Thanks to this approximation, the information is complemented, and the outcome will increment the quality in any Marketing/Sales initiative. The goal of this article is to explore the different factors grouped by three main domains within the impact of service quality, from a consumer’s perspective, in both on-line and off-line retailing sector.  Secondly, we plan to go a step further and extract base guidelines about previous analysis for designing CRM’s solutions focused on the loyalty of the customers for a specific retailing sector and its product: Sports Running Shoes.

scholarly journals Thiol-based switching mechanisms of stress-sensing chaperones

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Kathrin Ulrich ◽  
Blanche Schwappach ◽  
Ursula Jakob
Keyword(s):  
Oxidative Stress ◽  
Environmental Changes ◽  
Stress Conditions ◽  
Stress Exposure ◽  
Atp Levels ◽  
Protein Functions ◽  
Activation Mechanisms ◽  
Client Proteins ◽  
Stress Sensing ◽  
Redox Switches

AbstractThiol-based redox switches evolved as efficient post-translational regulatory mechanisms that enable individual proteins to rapidly respond to sudden environmental changes. While some protein functions need to be switched off to save resources and avoid potentially error-prone processes, protective functions become essential and need to be switched on. In this review, we focus on thiol-based activation mechanisms of stress-sensing chaperones. Upon stress exposure, these chaperones convert into high affinity binding platforms for unfolding proteins and protect cells against the accumulation of potentially toxic protein aggregates. Their chaperone activity is independent of ATP, a feature that becomes especially important under oxidative stress conditions, where cellular ATP levels drop and canonical ATP-dependent chaperones no longer operate. Vice versa, reductive inactivation and substrate release require the restoration of ATP levels, which ensures refolding of client proteins by ATP-dependent foldases. We will give an overview over the different strategies that cells evolved to rapidly increase the pool of ATP-independent chaperones upon oxidative stress and provide mechanistic insights into how stress conditions are used to convert abundant cellular proteins into ATP-independent holding chaperones.

scholarly journals Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2421
Author(s):  
Saray Tabak ◽  
Sofia Schreiber-Avissar ◽  
Elie Beit-Yannai
Keyword(s):  
Oxidative Stress ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Additional Treatment ◽  
Type I ◽  
Open Angle ◽  
Outflow Resistance ◽  
Stress Injury

Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.

Past testate amoeba communities in landslide mountain fens (Polish Carpathians): The relationship between shell types and sediment

The Holocene ◽  
2021 ◽  
pp. 095968362199464
Author(s):  
Katarzyna Marcisz ◽  
Krzysztof Buczek ◽  
Mariusz Gałka ◽  
Włodzimierz Margielewski ◽  
Matthieu Mulot ◽  
...  
Keyword(s):  
Environmental Changes ◽  
Testate Amoebae ◽  
Mineral Matter ◽  
Testate Amoeba ◽  
Run Off ◽  
Number Of Factors ◽  
Depth To Water Table ◽  
Polish Carpathians ◽  
The Relationship

Landslide mountain fens formed in landslide depressions are dynamic environments as their development is disturbed by a number of factors, for example, landslides, slopewash, and surface run-off. These processes lead to the accumulation of mineral material and wood in peat. Disturbed peatlands are interesting archives of past environmental changes, but they may be challenging for providing biotic proxy-based quantitative reconstructions. Here we investigate long-term changes in testate amoeba communities from two landslide mountain fens – so far an overlooked habitat for testate amoeba investigations. Our results show that abundances of testate amoebae are extremely low in this type of peatlands, therefore not suitable for providing quantitative depth-to-water table reconstructions. However, frequent shifts of dominant testate amoeba species reflect dynamic lithological situation of the studied fens. We observed that high and stable mineral matter input into the peatlands was associated with high abundances of species producing agglutinated (xenosomic) as well as idiosomic shells which prevailed in the testate amoeba communities in both analyzed profiles. This is the first study that explores testate amoebae of landslide mountain fens in such detail, providing novel information about microbial communities of these ecosystems.

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