scholarly journals A Metabolic Profiling Analysis Revealed a Primary Metabolism Reprogramming in Arabidopsis glyI4 Loss-of-Function Mutant

Plants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2464
Author(s):  
Silvia Proietti ◽  
Laura Bertini ◽  
Gaia Salvatore Falconieri ◽  
Ivan Baccelli ◽  
Anna Maria Timperio ◽  
...  
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Stomatal Closure ◽  
Primary Metabolism ◽  
Loss Of Function ◽  
Cytotoxic Compound ◽  
System A ◽  
Metabolic Profiling Analysis ◽  
The Impact ◽  
Energy Maintenance ◽  
Metabolomic Approach

Methylglyoxal (MG) is a cytotoxic compound often produced as a side product of metabolic processes such as glycolysis, lipid peroxidation, and photosynthesis. MG is mainly scavenged by the glyoxalase system, a two-step pathway, in which the coordinate activity of GLYI and GLYII transforms it into D-lactate, releasing GSH. In Arabidopsis thaliana, a member of the GLYI family named GLYI4 has been recently characterized. In glyI4 mutant plants, a general stress phenotype characterized by compromised MG scavenging, accumulation of reactive oxygen species (ROS), stomatal closure, and reduced fitness was observed. In order to shed some light on the impact of gly4 loss-of-function on plant metabolism, we applied a high resolution mass spectrometry-based metabolomic approach to Arabidopsis Col-8 wild type and glyI4 mutant plants. A compound library containing a total of 70 metabolites, differentially synthesized in glyI4 compared to Col-8, was obtained. Pathway analysis of the identified compounds showed that the upregulated pathways are mainly involved in redox reactions and cellular energy maintenance, and those downregulated in plant defense and growth. These results improved our understanding of the impacts of glyI4 loss-of-function on the general reprogramming of the plant’s metabolic landscape as a strategy for surviving under adverse physiological conditions.

scholarly journals GLYI4 Plays A Role in Methylglyoxal Detoxification and Jasmonate-Mediated Stress Responses in Arabidopsis thaliana

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 635 ◽  
Author(s):  
Silvia Proietti ◽  
Gaia Salvatore Falconieri ◽  
Laura Bertini ◽  
Ivan Baccelli ◽  
Elena Paccosi ◽  
...  
Keyword(s):  
Stress Responses ◽  
Genome Wide Association Study ◽  
Pathogenic Fungus ◽  
Stomatal Closure ◽  
Defense Responses ◽  
Primary Metabolism ◽  
Lower Efficiency ◽  
Biotic Stresses ◽  
A Genome ◽  
The Impact

Plant hormones play a central role in various physiological functions and in mediating defense responses against (a)biotic stresses. In response to primary metabolism alteration, plants can produce also small molecules such as methylglyoxal (MG), a cytotoxic aldehyde. MG is mostly detoxified by the combined actions of the enzymes glyoxalase I (GLYI) and glyoxalase II (GLYII) that make up the glyoxalase system. Recently, by a genome-wide association study performed in Arabidopsis, we identified GLYI4 as a novel player in the crosstalk between jasmonate (JA) and salicylic acid (SA) hormone pathways. Here, we investigated the impact of GLYI4 knock-down on MG scavenging and on JA pathway. In glyI4 mutant plants, we observed a general stress phenotype, characterized by compromised MG scavenging, accumulation of reactive oxygen species (ROS), stomatal closure, and reduced fitness. Accumulation of MG in glyI4 plants led to lower efficiency of the JA pathway, as highlighted by the increased susceptibility of the plants to the pathogenic fungus Plectospherella cucumerina. Moreover, MG accumulation brought about a localization of GLYI4 to the plasma membrane, while MeJA stimulus induced a translocation of the protein into the cytoplasmic compartment. Collectively, the results are consistent with the hypothesis that GLYI4 is a hub in the MG and JA pathways.

Technology and Hospital Information System: A Case of Implementation of Electronic Clinical Records in Hospital Maternity Irene Neto in Lubango, Angola

2019 ◽  
Vol 10 (11) ◽  
pp. 1131-1135
Author(s):  
Tomas Hambili Paulo Sanjuluca ◽  
◽  
Ricardo Correia ◽  
Anabela Antunes de Almeida ◽  
Ana Gloria Diaz Martinez ◽  
...  
Keyword(s):  
Maternity Hospital ◽  
Management Support ◽  
Retrospective Case ◽  
System A ◽  
Clinical Records ◽  
Retrospective Case Study ◽  
The Impact ◽  
And Child Health

Introduction: In order to have a good assessment of the quality of maternal and child health care, it is essential that there is up-to-date and reliable information. Objective: To evaluate the impact of the implementation of a computerized database of clinical processes in the admission, archive and medical statistics section, of Maternity hospital Irene Neto/Lubango-Angola. Methodology: A descriptive study with a quantitative and qualitative approach to carry out a retrospective case study deliveries and newborns, records from 2014 to 2017. Final considerations: The implementation of this project may contribute to the improvement of clinical management support management of the hospital as well as facilitating access to information for research and scientific production.

The Impact of Political Transition on Ghana’s Educational System. A Case Study of the 4th Republic

2018 ◽  
Author(s):  
Emmanuel Owusu-Kwarteng ◽  
Prince Opoku ◽  
Gershon Dagba ◽  
Mark Amankwa
Keyword(s):  
Educational System ◽  
Political Transition ◽  
System A ◽  
The Impact

Impact Load Buffering Method Based on Stress Wave Attenuation Principle

2019 ◽  
Vol 11 (02) ◽  
pp. 1950019 ◽  
Author(s):  
Lin Gan ◽  
He Zhang ◽  
Cheng Zhou ◽  
Lin Liu
Keyword(s):  
Stress Wave ◽  
Wave Attenuation ◽  
Impact Load ◽  
Dynamics Simulation ◽  
Scanning System ◽  
Isolation Method ◽  
Element Analysis ◽  
System A ◽  
High Emission ◽  
The Impact

Rotating scanning motor is the important component of synchronous scanning laser fuze. High emission overload environment in the conventional ammunition has a serious impact on the reliability of the motor. Based on the theory that the buffer pad can attenuate the impact stress wave, a new motor buffering Isolation Method is proposed. The dynamical model of the new buffering isolation structure is established by ANSYS infinite element analysis software to do the nonlinear impact dynamics simulation of rotating scanning motor. The effectiveness of Buffering Isolation using different materials is comparatively analyzed. Finally, the Macht hammer impact experiment is done, the results show that in the experience of the 70,000[Formula: see text]g impact acceleration, the new buffering Isolation method can reduce the impact load about 15 times, which can effectively alleviate the plastic deformation of rotational scanning motor and improve the reliability of synchronization scanning system. A new method and theoretical basis of anti-high overload research for Laser Fuze is presented.

Statistical Approaches to Structural Change in Regional Interindustry Models

1986 ◽  
Vol 18 (9) ◽  
pp. 1189-1207
Author(s):  
B Ó Huallacháin
Keyword(s):  
Structural Change ◽  
Structural Changes ◽  
Washington State ◽  
Multivariate Statistical Analyses ◽  
Input Output ◽  
Multivariate Statistical ◽  
State Data ◽  
System A ◽  
Statistical Approaches ◽  
The Impact

The conventional approach to assessing structural change in regional input – output tables is to measure the impact of coefficient change on the estimation of outputs and multipliers. The methods developed and tested in this paper focus exclusively on the coefficients. Univariate and multivariate statistical analyses can be used to identify and measure various types of changes ranging from coefficient instability to changes in interindustry relationships as a system. A distinction is made between structural changes in input relationships and those in output relationships. The methods are tested by using Washington State data for the years 1963 and 1967. The results are compared with previous analyses of change in these data.

scholarly journals ATP13A2 Regulates Cellular α-Synuclein Multimerization, Membrane Association, and Externalization

2021 ◽  
Vol 22 (5) ◽  
pp. 2689
Author(s):  
Jianmin Si ◽  
Chris Van den Haute ◽  
Evy Lobbestael ◽  
Shaun Martin ◽  
Sarah van Veen ◽  
...  
Keyword(s):  
Membrane Integrity ◽  
Ubiquitin Proteasome System ◽  
Regulatory Function ◽  
Membrane Association ◽  
Loss Of Function ◽  
Atypical Form ◽  
Polyamine Transport ◽  
Independent Functions ◽  
Ubiquitin Proteasome ◽  
The Impact

ATP13A2, a late endo-/lysosomal polyamine transporter, is implicated in a variety of neurodegenerative diseases, including Parkinson’s disease and Kufor–Rakeb syndrome, an early-onset atypical form of parkinsonism. Loss-of-function mutations in ATP13A2 result in lysosomal deficiency as a consequence of impaired lysosomal export of the polyamines spermine/spermidine. Furthermore, accumulating evidence suggests the involvement of ATP13A2 in regulating the fate of α-synuclein, such as cytoplasmic accumulation and external release. However, no consensus has yet been reached on the mechanisms underlying these effects. Here, we aimed to gain more insight into how ATP13A2 is linked to α-synuclein biology in cell models with modified ATP13A2 activity. We found that loss of ATP13A2 impairs lysosomal membrane integrity and induces α-synuclein multimerization at the membrane, which is enhanced in conditions of oxidative stress or exposure to spermine. In contrast, overexpression of ATP13A2 wildtype (WT) had a protective effect on α-synuclein multimerization, which corresponded with reduced αsyn membrane association and stimulation of the ubiquitin-proteasome system. We also found that ATP13A2 promoted the secretion of α-synuclein through nanovesicles. Interestingly, the catalytically inactive ATP13A2 D508N mutant also affected polyubiquitination and externalization of α-synuclein multimers, suggesting a regulatory function independent of the ATPase and transport activity. In conclusion, our study demonstrates the impact of ATP13A2 on α-synuclein multimerization via polyamine transport dependent and independent functions.

A Melanocortin-4 Receptor Agonist Induces Skin and Hair Pigmentation in Patients with Monogenic Mutations in the Leptin-Melanocortin Pathway

2021 ◽  
pp. 1-10
Author(s):  
Varvara Kanti ◽  
Lia Puder ◽  
Irina Jahnke ◽  
Philipp Maximilian Krabusch ◽  
Jan Kottner ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Skin Pigmentation ◽  
Gene Mutations ◽  
Continuous Treatment ◽  
Whole Body ◽  
Hair Color ◽  
Phase 2 ◽  
Loss Of Function ◽  
The Impact ◽  
Over Time

<b><i>Background and Objectives:</i></b> Gene mutations within the leptin-melanocortin signaling pathway lead to severe early-onset obesity. Recently, a phase 2 trial evaluated new pharmacological treatment options with the MC4R agonist <i>setmelanotide</i> in patients with mutations in the genes encoding proopiomelanocortin (POMC) and leptin receptor (LEPR). During treatment with <i>setmelanotide,</i> changes in skin pigmentation were observed, probably due to off-target effects on the closely related melanocortin 1 receptor (MC1R). Here, we describe in detail the findings of dermatological examinations and measurements of skin pigmentation during this treatment over time and discuss the impact of these changes on patient safety. <b><i>Methods:</i></b> In an investigator-initiated, phase 2, open-label pilot study, 2 patients with loss-of-function POMC gene mutations and 3 patients with loss-of-function variants in LEPR were treated with the MC4R agonist <i>setmelanotide</i>. Dermatological examination, dermoscopy, whole body photographic documentation, and spectrophotometric measurements were performed at screening visit and approximately every 3 months during the course of the study. <b><i>Results:</i></b> We report the results of a maximum treatment duration of 46 months. Skin pigmentation increased in all treated patients, as confirmed by spectrophotometry. During continuous treatment, the current results indicate that elevated tanning intensity levels may stabilize over time. Lips and nevi also darkened. In red-haired study participants, hair color changed to brown after initiation of <i>setmelanotide</i> treatment. <b><i>Discussion:</i></b> <i>Setmelanotide</i> treatment leads to skin tanning and occasionally hair color darkening in both POMC- and LEPR-deficient patients. No malignant skin changes were observed in the patients of this study. However, the results highlight the importance of regular skin examinations before and during MC4R agonist treatment.

scholarly journals Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas Duflot ◽  
Charlotte Laurent ◽  
Anne Soudey ◽  
Xavier Fonrose ◽  
Mouad Hamzaoui ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Kidney Transplant ◽  
Plasma Levels ◽  
Renal Allograft ◽  
Transplant Recipients ◽  
Loss Of Function ◽  
Kidney Transplant Recipients ◽  
Allograft Dysfunction ◽  
Allograft Function ◽  
The Impact

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.

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