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31.
Syed Muhammad Hamid Mevlut Citir Erdem Murat Terzi Ismail Cimen Zehra Yildirim Asli Ekin Dogan Begum Kocaturk Umut Inci Onat Moshe Arditi Christian Weber Alexis TraynorKaplan Carsten Schultz Ebru Erbay 《EMBO reports》2020,21(12)
The ER‐bound kinase/endoribonuclease (RNase), inositol‐requiring enzyme‐1 (IRE1), regulates the phylogenetically most conserved arm of the unfolded protein response (UPR). However, the complex biology and pathology regulated by mammalian IRE1 cannot be fully explained by IRE1’s one known, specific RNA target, X box‐binding protein‐1 (XBP1) or the RNA substrates of IRE1‐dependent RNA degradation (RIDD) activity. Investigating other specific substrates of IRE1 kinase and RNase activities may illuminate how it performs these diverse functions in mammalian cells. We report that macrophage IRE1 plays an unprecedented role in regulating phosphatidylinositide‐derived signaling lipid metabolites and has profound impact on the downstream signaling mediated by the mammalian target of rapamycin (mTOR). This cross‐talk between UPR and mTOR pathways occurs through the unconventional maturation of microRNA (miR) 2137 by IRE1’s RNase activity. Furthermore, phosphatidylinositol (3,4,5) phosphate (PI(3,4,5)P3) 5‐phosphatase‐2 (INPPL1) is a direct target of miR‐2137, which controls PI(3,4,5)P3 levels in macrophages. The modulation of cellular PI(3,4,5)P3/PIP2 ratio and anabolic mTOR signaling by the IRE1‐induced miR‐2137 demonstrates how the ER can provide a critical input into cell growth decisions. 相似文献
32.
33.
Ramon Velazquez Eric Ferreira Sara Knowles Chaya Fux Alexis Rodin Wendy Winslow Salvatore Oddo 《Aging cell》2019,18(6)
Currently, there are no effective therapies to ameliorate the pathological progression of Alzheimer's disease (AD). Evidence suggests that environmental factors may contribute to AD. Notably, dietary nutrients are suggested to play a key role in mediating mechanisms associated with brain function. Choline is a B‐like vitamin nutrient found in common foods that is important in various cell functions. It serves as a methyl donor and as a precursor for production of cell membranes. Choline is also the precursor for acetylcholine, a neurotransmitter which activates the alpha7 nicotinic acetylcholine receptor (α7nAchR), and also acts as an agonist for the Sigma‐1 R (σ1R). These receptors regulate CNS immune response, and their dysregulation contributes to AD pathogenesis. Here, we tested whether dietary choline supplementation throughout life reduces AD‐like pathology and rescues memory deficits in the APP/PS1 mouse model of AD. We exposed female APP/PS1 and NonTg mice to either a control choline (1.1 g/kg choline chloride) or a choline‐supplemented diet (5.0 g/kg choline chloride) from 2.5 to 10 months of age. Mice were tested in the Morris water maze to assess spatial memory followed by neuropathological evaluation. Lifelong choline supplementation significantly reduced amyloid‐β plaque load and improved spatial memory in APP/PS1 mice. Mechanistically, these changes were linked to a decrease of the amyloidogenic processing of APP, reductions in disease‐associated microglial activation, and a downregulation of the α7nAch and σ1 receptors. Our results demonstrate that lifelong choline supplementation produces profound benefits and suggest that simply modifying diet throughout life may reduce AD pathology. 相似文献
34.
Andrea Evangelina Arcángel Emiliano Alexis Rodríguez Juan Francisco Saad Paula de la Barra Maite Andrea Narvarte Lorena Pía Storero Patricio Javier Pereyra 《Journal of phycology》2023,59(6):1310-1322
Population dynamics can be influenced by physical and biological factors, particularly in stressful environments. Introduced species usually have great physiological plasticity, resulting in populations with different traits. Undaria pinnatifida, a macroalga originally described from northeast Asia, was introduced in Northern Patagonia, Argentina (San Matías Gulf) around 2010. To describe the spatio-temporal variability in population structure and morphometry of U. pinnatifida, we conducted monthly field samplings for 2 years at the intertidal area of two contrasting sites in the San Matías Gulf. Individuals of U. pinnatifida were classified by developmental stage, and their morpho-gravimetric variables were measured. In both intertidal sites juveniles were found in higher proportion during austral autumn and grew and matured during the autumn-winter months (from May onwards), and individuals senesced during early austral summer (December and January). Conversely, density and biomass were largely different between sites, and individuals showed slight morphological variability between sites. Environmental (e.g., nutrient concentration, available substrate) and biological factors (e.g., facilitation, competition) may explain the observed differences. Since there is not a macroalga with U. pinnatifida morphometrical characteristics in the intertidal environments of San Matías Gulf, studying this recent introduction gives us a better understanding of its potential ecological effects. 相似文献
35.
Andrés Ritter Emmanuelle Com Alexis Bazire Marina Dos Santos Goncalves Ludovic Delage Gaël Le Pennec Charles Pineau Catherine Dreanno Chantal Compère Alain Dufour 《Proteomics》2012,12(21):3180-3192
Bacterial biofilm development is conditioned by complex processes involving bacterial attachment to surfaces, growth, mobility, and exoproduct production. The marine bacterium Pseudoalteromonas sp. strain D41 is able to attach strongly onto a wide variety of substrates, which promotes subsequent biofilm development. Study of the outer‐membrane and total soluble proteomes showed ten spots with significant intensity variations when this bacterium was grown in biofilm compared to planktonic cultures. MS/MS de novo sequencing analysis allowed the identification of four outer‐membrane proteins of particular interest since they were strongly induced in biofilms. These proteins are homologous to a TonB‐dependent receptor (TBDR), to the OmpW and OmpA porins, and to a type IV pilus biogenesis protein (PilF). Gene expression assays by quantitative RT‐PCR showed that the four corresponding genes were upregulated during biofilm development on hydrophobic and hydrophilic surfaces. The Pseudomonas aeruginosa mutants unable to produce any of the OmpW, OmpA, and PilF homologues yielded biofilms with lower biovolumes and altered architectures, confirming the involvement of these proteins in the biofilm formation process. Our results indicate that Pseudoalteromonas sp. D41 shares biofilm formation mechanisms with human pathogenic bacteria, but also relies on TBDR, which might be more specific to the marine environment. 相似文献
36.
Benjamin Deneu Maximilien Servajean Pierre Bonnet Christophe Botella Franois Munoz Alexis Joly 《PLoS computational biology》2021,17(4)
Convolutional Neural Networks (CNNs) are statistical models suited for learning complex visual patterns. In the context of Species Distribution Models (SDM) and in line with predictions of landscape ecology and island biogeography, CNN could grasp how local landscape structure affects prediction of species occurrence in SDMs. The prediction can thus reflect the signatures of entangled ecological processes. Although previous machine-learning based SDMs can learn complex influences of environmental predictors, they cannot acknowledge the influence of environmental structure in local landscapes (hence denoted “punctual models”). In this study, we applied CNNs to a large dataset of plant occurrences in France (GBIF), on a large taxonomical scale, to predict ranked relative probability of species (by joint learning) to any geographical position. We examined the way local environmental landscapes improve prediction by performing alternative CNN models deprived of information on landscape heterogeneity and structure (“ablation experiments”). We found that the landscape structure around location crucially contributed to improve predictive performance of CNN-SDMs. CNN models can classify the predicted distributions of many species, as other joint modelling approaches, but they further prove efficient in identifying the influence of local environmental landscapes. CNN can then represent signatures of spatially structured environmental drivers. The prediction gain is noticeable for rare species, which open promising perspectives for biodiversity monitoring and conservation strategies. Therefore, the approach is of both theoretical and practical interest. We discuss the way to test hypotheses on the patterns learnt by CNN, which should be essential for further interpretation of the ecological processes at play. 相似文献
37.
Dunne J Caron A Menu P Alayash AI Buehler PW Wilson MT Silaghi-Dumitrescu R Faivre B Cooper CE 《The Biochemical journal》2006,399(3):513-524
Haemoglobin initiates free radical chemistry. In particular, the interactions of peroxides with the ferric (met) species of haemoglobin generate two strong oxidants: ferryl iron and a protein-bound free radical. We have studied the endogenous defences to this reactive chemistry in a rabbit model following 20% exchange transfusion with cell-free haemoglobin stabilized in tetrameric form [via cross-linking with bis-(3,5-dibromosalicyl)fumarate]. The transfusate contained 95% oxyhaemoglobin, 5% methaemoglobin and 25 microM free iron. EPR spectroscopy revealed that the free iron in the transfusate was rendered redox inactive by rapid binding to transferrin. Methaemoglobin was reduced to oxyhaemoglobin by a slower process (t(1/2) = 1 h). No globin-bound free radicals were detected in the plasma. These redox defences could be fully attributed to a novel multifunctional role of plasma ascorbate in removing key precursors of oxidative damage. Ascorbate is able to effectively reduce plasma methaemoglobin, ferryl haemoglobin and globin radicals. The ascorbyl free radicals formed are efficiently re-reduced by the erythrocyte membrane-bound reductase (which itself uses intra-erythrocyte ascorbate as an electron donor). As well as relating to the toxicity of haemoglobin-based oxygen carriers, these findings have implications for situations where haem proteins exist outside the protective cell environment, e.g. haemolytic anaemias, subarachnoid haemorrhage, rhabdomyolysis. 相似文献
38.
Yelton AP Thomas BC Simmons SL Wilmes P Zemla A Thelen MP Justice N Banfield JF 《PLoS computational biology》2011,7(10):e1002230
During microbial evolution, genome rearrangement increases with increasing sequence divergence. If the relationship between synteny and sequence divergence can be modeled, gene clusters in genomes of distantly related organisms exhibiting anomalous synteny can be identified and used to infer functional conservation. We applied the phylogenetic pairwise comparison method to establish and model a strong correlation between synteny and sequence divergence in all 634 available Archaeal and Bacterial genomes from the NCBI database and four newly assembled genomes of uncultivated Archaea from an acid mine drainage (AMD) community. In parallel, we established and modeled the trend between synteny and functional relatedness in the 118 genomes available in the STRING database. By combining these models, we developed a gene functional annotation method that weights evolutionary distance to estimate the probability of functional associations of syntenous proteins between genome pairs. The method was applied to the hypothetical proteins and poorly annotated genes in newly assembled acid mine drainage Archaeal genomes to add or improve gene annotations. This is the first method to assign possible functions to poorly annotated genes through quantification of the probability of gene functional relationships based on synteny at a significant evolutionary distance, and has the potential for broad application. 相似文献
39.
An experimental set-up which enabled non-invasive, real-time reactive oxygen species (ROS) visualization on a whole plant
level was constructed. In the test organism, Lemna minor L. (common duckweed), apoplastic and symplastic oxidative stress was evaluated by exposure to menadione (50 μM), menadione (50 μM) + ascorbate (100 μM) or neither for control. Menadione (50 μM) caused a statistically significant increase in H2DCFDA fluorescence in the apoplast after 60 minutes of exposure. The addition of ascorbate (100 μM) in the test medium significantly decreased apoplastic oxidative stress. 50 μM menadione caused an increase in symplastic H2DCFDA fluorescence in 57% of fronds. The exposure of L. minor plants to both menadione and ascorbate decreased the rate of fluorescence intensity accumulation in the symplast to control
levels. The method has proven to be quick and straightforward and could be applied to a range of chemicals in various physiological
and toxicological plant studies. The advantages of the set-up and different possible artefacts are discussed. 相似文献
40.
Katsanou ES Halabalaki M Aligiannis N Mitakou S Skaltsounis AL Alexi X Pratsinis H Alexis MN 《The Journal of steroid biochemistry and molecular biology》2007,104(3-5):228-236
Although 2-arylbenzofuran phytoalexins are known for decades, their anticancer activity has not been studied systematically. We have previously reported on the isolation and the estrogen receptor (ER) modulation properties of three new 2-arylbenzofurans from Onobrychis ebenoides, ebenfuran I [2-(2,4-dihydroxyphenyl)-5-hydroxy-6-methoxy-benzofuran], ebenfuran II [2-(2,4-dihydroxyphenyl)-3-formyl-4-hydroxy-6-methoxy-benzofuran] and ebenfuran III [2-(2,4-dihydroxyphenyl)-3-formyl-4-hydroxy-6-methoxy-5-(3-methyl-buten-2-yl)-benzofuran]. We now show that, while I and II could stimulate the proliferation of MCF-7 cells, III was inhibitory in a proliferation-dependent manner. III inhibited the growth of all human cancer cells examined, regardless of ER or multidrug resistance status. Estradiol rendered MCF-7 cells more sensitive to III, and this coincided with the ability of the hormone at concentrations ≥0.1 nM to bind to the ER of the cells and stimulate their proliferation in the presence of III. Cell proliferation stimulating concentrations of I and II also enhanced the effect of III on MCF-7 cells. However, dehydroepiandrosterone and dihydrotestosterone were ineffective in this respect. III-treated MCF-7 cells exhibited G1 phase arrest followed by detachment-induced cell death and/or apoptosis in the adherent fraction, pronounced induction of Bax and suppression of estradiol induction of Bcl-2. Our data indicate that the largely unexplored pool of benzofuran phytoalexins includes entities potentially suitable for chemoprevention and treatment of human cancer. 相似文献