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1.
Background
Rhodopsin mutations are associated with the autosomal dominant form of retinitis pigmentosa. T17M mutation in rhodopsin predisposes cells to endoplasmic reticulum (ER) stress and induces cell death. This study aimed to examine whether chemical chaperone 4-phenylbutyrate prevents ER stress induced by rhodopsin T17M.Results
ARPE-19 cells were transfected with myc-tagged wild-type (WT) and T17M rhodopsin constructs. Turnover of WT and T17M rhodopsin was measured by cycloheximide chase analysis. The activity of ubiquitin-proteasome system was evaluated by GFPU reporter. We found that T17M rhodopsin was misfolded, ubiqutinated and eliminated by ER-associated degradation pathway (ERAD) in ARPE-19 cells. Accumulated T17M rhodopsin induced unfolded protein response, but had no effect on the activity of ubiquitin proteasome system. Moreover, chemical chaperone 4-phenylbutyrate facilitated the turnover of T17M rhodopsin and prevented apoptosis and ER stress induced by T17M rhodopsin.Conclusions
Chemical chaperone could attenuate UPR signaling and ER stress induced by T17M rhodopsin and has potential therapeutic significance for retinitis pigmentosa.2.
Songwen Tan Xuncai Chen Chunzhi Cui Yang Hou Weiguo Li Hong You 《Biotechnology letters》2017,39(1):91-96
Objective
To develop a method to treat saline phenolic wastewater in a biological contact oxidation reactor (BCOR) with immobilized cells of a marine microorganism, Oceanimonas sp., isolated from seawater.Results
Cells were immobilized on fibre carriers in the BCOR. Saline wastewater with phenol at 1.5 g/l and NaCl at 6 % (w/v) was treated. In continuous assays, 99 % removal of phenol was achieved and a kinetic model for the phenol degradation is presented based on Monod’s equation.Conclusion
The BOCR system using immobilized cells of Oceanimonas efficiently treats saline phenolic wastewaters without having decrease the salinity of the wastewater.3.
Yi-Chao Lee Wan-Chen Huang Jiann-Her Lin Tzu-Jen Kao Hui-Ching Lin Kuen-Haur Lee Hsin-Chuan Lin Che-Kun James Shen Wen-Chang Chang Chi-Chen Huang 《Journal of biomedical science》2018,25(1):76
Background
The brain predominantly expressed RING finger protein, Znf179, is known to be important for embryonic neuronal differentiation during brain development. Downregulation of Znf179 has been observed in motor neurons of adult mouse models for amyotrophic lateral sclerosis (ALS), yet the molecular function of Znf179 in neurodegeneration has never been previously described. Znf179 contains the classical C3HC4 RING finger domain, and numerous proteins containing C3HC4 RING finger domain act as E3 ubiquitin ligases. Hence, we are interested to identify whether Znf179 possesses E3 ligase activity and its role in ALS neuropathy.Methods
We used in vivo and in vitro ubiquitination assay to examine the E3 ligase autoubiquitination activity of Znf179 and its effect on 26S proteasome activity. To search for the candidate substrates of Znf179, we immunoprecipitated Znf179 and subjected to mass spectrometry (MS) analysis to identify its interacting proteins. We found that ALS/ FTLD-U (frontotemporal lobar degeneration (FTLD) with ubiquitin inclusions)-related neurodegenerative TDP-43 protein is the E3 ligase substrate of Znf179. To further clarify the role of E3 ubiquitin ligase Znf179 in neurodegenerative TDP-43-UBI (ubiquitinated inclusions) (+) proteinopathy, the effect of Znf179-mediated TDP-43 polyubiquitination on TDP-43 protein stability, aggregate formation and nucleus/cytoplasm mislocalization were evaluated in vitro cell culture system and in vivo animal model.Results
Here we report that Znf179 is a RING E3 ubiquitin ligase which possesses autoubiquitination feature and regulates 26S proteasome activity through modulating the protein expression levels of 19S/20S proteasome subunits. Our immunoprecipitation assay and MS analysis results revealed that the neuropathological TDP-43 protein is one of its E3 ligase substrate. Znf179 interactes with TDP-43 protein and mediates polyubiquitination of TDP-43 in vitro and in vivo. In neurodegenerative TDP-43 proteinopathy, we found that Znf179-mediated polyubiquitination of TDP-43 accelerates its protein turnover rate and attenuates insoluble pathologic TDP-43 aggregates, while knockout of Znf179 in mouse brain results in accumulation of insoluble TDP-43 and cytosolic TDP-43 inclusions in cortex, hippocampus and midbrain regions.Conclusions
Here we unveil the important role for the novel E3 ligase Znf179 in TDP-43-mediated neuropathy, and provide a potential therapeutic strategy for combating ALS/ FTLD-U neurodegenerative pathologies.4.
Background
Cullin-RING E3 ubiquitin ligase complexes play a central role in targeting cellular proteins for ubiquitination-dependent protein turnover through 26S proteasome. Cullin-2 is a member of the Cullin family, and it serves as a scaffold protein for Elongin B and C, Rbx1 and various substrate recognition receptors to form E3 ubiquitin ligases.Main body of the abstract
First, the composition, structure and the regulation of Cullin-2 based E3 ubiquitin ligases were introduced. Then the targets, the biological functions of complexes that use VHL, Lrr-1, Fem1b, Prame, Zyg-11, BAF250, Rack1 as substrate targeting subunits were described, and their involvement in diseases was discussed. A small molecule inhibitor of Cullins as a potential anti-cancer drug was introduced. Furthermore, proteins with VHL box that might bind to Cullin-2 were described. Finally, how different viral proteins form E3 ubiquitin ligase complexes with Cullin-2 to counter host viral defense were explained.Conclusions
Cullin-2 based E3 ubiquitin ligases, using many different substrate recognition receptors, recognize a number of substrates and regulate their protein stability. These complexes play critical roles in biological processes and diseases such as cancer, germline differentiation and viral defense. Through the better understanding of their biology, we can devise and develop new therapeutic strategies to treat cancers, inherited diseases and viral infections.5.
Alicja Sznarkowska Anna Kostecka Anna Kawiak Pilar Acedo Mattia Lion Alberto Inga Joanna Zawacka-Pankau 《Cell division》2018,13(1):10
Background
The p73 protein is a tumor suppressor that shares structural and functional similarity with p53. p73 is expressed in two major isoforms; the TA isoform that interacts with p53 pathway, thus acting as tumor suppressor and the N-terminal truncated ΔN isoform that inhibits TAp73 and p53 and thus, acts as an oncogene.Results
By employing a drug repurposing approach, we found that protoporphyrin IX (PpIX), a metabolite of aminolevulinic acid applied in photodynamic therapy of cancer, stabilizes TAp73 and activates TAp73-dependent apoptosis in cancer cells lacking p53. The mechanism of TAp73 activation is via disruption of TAp73/MDM2 and TAp73/MDMX interactions and inhibition of TAp73 degradation by ubiquitin ligase Itch. Finally, PpIX showed potent antitumor effect and inhibited the growth of xenograft human tumors in mice.Conclusion
Our findings may in future contribute to the successful repurposing of PpIX into clinical practice.6.
Gloria Gutiérrez-Venegas Alfredo Torras-Ceballos Juan Arturo Gómez-Mora Berenice Fernández-Rojas 《Cellular & molecular biology letters》2017,22(1):19
Background
One of the microorganisms from dental plaque associated with severe inflammatory responses in infectious endocarditis is Porphyromonas gingivalis. It is a Gram-negative bacteria harvested from chronic periodontitis patients. Lipopolysaccharide (LPS) obtained from P. gingivalis promotes the expressions of interleukin-1 (IL-1), IL-6 and tumor necrosis factor alpha (TNF-α). Flavonoids are thought to participate in processes that control inflammation, such as the expression of cyclooxygenase-2 (COX-2).Methods
We investigated the effects of luteolin, quercetin, genistein and quercetagetin on cardiomyoblasts treated with LPS alone or in combination with following inhibitors p38 (SB203580), ERK (PD98059), JNK (SP600125) and PKC (Calphostin C) for 1 h. The kinase activation and COX-2 expression levels were determined at the gene and protein levels.Results
These flavonoids are considered to inhibit the activation of mitogen-activated protein kinase (MAPK) and the degradation of inhibitor of kappa B-alpha (IκB-α). They also play a role in COX-2 expression.Conclusion
We conclude that the tested flavonoids inhibit inflammatory responses induced by LPS in H9c2 cells.7.
Katie E. Hillyer Daniel Dias Adrian Lutz Ute Roessner Simon K. Davy 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):12
Introduction
Rising seawater temperatures are threatening the persistence of coral reefs; where above critical thresholds, thermal stress results in a breakdown of the coral-dinoflagellate symbiosis and the loss of algal symbionts (coral bleaching). As symbiont-derived organic products typically form a major portion of host energy budgets, this has major implications for the fitness and persistence of symbiotic corals.Objectives
We aimed to determine change in autotrophic carbon fate within individual compounds and downstream metabolic pathways in a coral symbiosis exposed to varying degrees of thermal stress and bleaching.Methods
We applied gas chromatography–mass spectrometry coupled to a stable isotope tracer (13C), to track change in autotrophic carbon fate, in symbiont and host individually, following exposure to elevated water temperature.Results
Thermal stress resulted in partner-specific changes in carbon fate, which progressed with heat stress duration. We detected modifications to carbohydrate and fatty acid metabolism, lipogenesis, and homeostatic responses to thermal, oxidative and osmotic stress. Despite pronounced photodamage, remaining in hospite symbionts continued to produce organic products de novo and translocate to the coral host. However as bleaching progressed, we observed minimal 13C enrichment of symbiont long-chain fatty acids, also reflected in 13C enrichment of host fatty acid pools.Conclusion
These data have major implications for our understanding of coral symbiosis function during bleaching. Our findings suggest that during early stage bleaching, remaining symbionts continue to effectively translocate a variety of organic products to the host, however under prolonged thermal stress there is likely a reduction in the quality of these products.8.
Jonas Barandun Fred F. Damberger Cyrille L. Delley Juerg Laederach Frédéric H. T. Allain Eilika Weber-Ban 《BMC structural biology》2017,17(1):1
Background
The post-translational modification pathway referred to as pupylation marks proteins for proteasomal degradation in Mycobacterium tuberculosis and other actinobacteria by covalently attaching the small protein Pup (prokaryotic ubiquitin-like protein) to target lysine residues. In contrast to the functionally analogous eukaryotic ubiquitin, Pup is intrinsically disordered in its free form. Its unfolded state allows Pup to adopt different structures upon interaction with different binding partners like the Pup ligase PafA and the proteasomal ATPase Mpa. While the disordered behavior of free Pup has been well characterized, it remained unknown whether Pup adopts a distinct structure when attached to a substrate.Results
Using a combination of NMR experiments and biochemical analysis we demonstrate that Pup remains unstructured when ligated to two well-established pupylation substrates targeted for proteasomal degradation in Mycobacterium tuberculosis, malonyl transacylase (FabD) and ketopantoyl hydroxylmethyltransferase (PanB). Isotopically labeled Pup was linked to FabD and PanB by in vitro pupylation to generate homogeneously pupylated substrates suitable for NMR analysis. The single target lysine of PanB was identified by a combination of mass spectroscopy and mutational analysis. Chemical shift comparison between Pup in its free form and ligated to substrate reveals intrinsic disorder of Pup in the conjugate.Conclusion
When linked to the proteasomal substrates FabD and PanB, Pup is unstructured and retains the ability to interact with its different binding partners. This suggests that it is not the conformation of Pup attached to these two substrates which determines their delivery to the proteasome, but the availability of the degradation complex and the depupylase.9.
Aims
We investigated potential mechanisms by which a seed microbiome recruited from vermicomposted dairy manure alters Pythium aphanidermatum zoospore mediated pathogenesis in cucumber.Methods
Bioassays were conducted to measure arrival of zoospores at the seed surface via qPCR and subsequent seedling disease incidence. Seed exudates were collected at relevant time points for use in zoospore microscopy assays. Metabolomic analysis was used to characterize seed exudates.Results
Microbes recruited by the germinating seed from a disease suppressive substrate within 8 hours of sowing prevented zoospore arrival at the seed surface, modified seed exudates and reduced disease incidence. In vitro exposure to microbially modified seed exudates altered zoospore homing responses and reduced both encystment and germination compared to control exudates. Combining modified and control exudates failed to restore zoospore attraction to levels observed with control exudates. Observed zoosporolytic activity of the modified exudates was unique to the ethyl acetate fraction and metabolomic analysis revealed several putative zoosporolytic compounds present at higher relative abundance when compared to control exudates.Conclusions
The observed disease suppression was likely due to the production of a specific zoosporolytic compound or set of compounds in the spermosphere by one or more members of the seed-recruited vermicompost microbiome.10.
11.
Florian Buettner Kyle Jay Harry Wischnewski Thomas Stadelmann Shady Saad Konstantins Jefimovs Madina Mansurova Juan Gerez Claus M. Azzalin Reinhard Dechant Alfredo J. Ibáñez 《Metabolomics : Official journal of the Metabolomic Society》2017,13(5):53
Introduction
The alternative lengthening of telomeres (ALT) mechanism was first observed in the model organism S. cerevisiae. Interestingly, this mechanism is necessary for the viability of some tumor cells. Unfortunately, its molecular underpinnings are not yet completely understood.Objective
Here, we combine carefully designed non-targeted mass spectrometry-based metabolomics experiments with a bioinformatics approach to characterize the ALT positive phenotype observed in yeast at the metabolomics level.Methods
We profiled the metabolome using mass spectrometry in yeast strains that have lost telomerase expression, as well as that in pre-senescence and the rescued states. To dissect unwanted technical variation from biologically relevant variation between these states, we used a two-step normalization strategy, i.e., first, an empirical Bayesian framework; and next, we corrected for second-order technical effects.Results
Our results show that ALT-positive yeast strains present two different types of metabolic responses to the genetically-induced telomerase dysfunction: (i) systemic and (ii) specific. The key-difference between these responses is that the systemic response lasts even after the yeast strains have been genetically rescued, while the specific response does not. Interestingly, these metabolic changes can be associated with generic stress responses (e.g., DNA damage) as well as specific responses like accelerated aging of early telomerase-inactivation.Conclusions
A mass spectrometry-based metabolomics approach reveals two distinct types of metabolomics response to telomerase dysfunction in yeast. By identifying these changes in protein (e.g., ARG7, and ARG1), and metabolite (e.g., dATP, and dDTP) amounts, we complement the available information on ALT at the genome-wide level.12.
Margarita Stritzler Ana Diez Tissera Gabriela Soto Nicolás Ayub 《Biotechnology letters》2018,40(9-10):1419-1423
Objectives
Identification of novel microbial factors contributing to plant protection against abiotic stress.Results
The genome of plant growth-promoting bacterium Pseudomonas fluorescens FR1 contains a short mobile element encoding a novel type of extracellular polyhydroxybutyrate (PHB) polymerase (PhbC) associated with a type I secretion system. Genetic analysis using a phbC mutant strain and plants showed that this novel extracellular enzyme is related to the PHB production in planta and suggests that PHB could be a beneficial microbial compound synthesized during plant adaptation to cold stress.Conclusion
Extracellular PhbC can be used as a new tool for improve crop production under abiotic stress.13.
14.
15.
Background and aims
Iron (Fe) toxicity is a wide-spread stress in lowland rice production. The aim of this study was to differentiate between responses to acute Fe stress during the vegetative stage and chronic Fe stress throughout the growing period.Methods
Six rice genotypes were tested in a semi-artificial greenhouse setup, in which acute (almost 1500 mg L?1 Fe in soil solution during the vegetative stage) and chronic (200 to 300 mg L?1 Fe throughout the season) Fe toxicity were simulated.Results
Acute Fe stress induced early development of heavy leaf bronzing, whereas moderate symptoms occurred in the chronic treatment throughout the season. Grain yields were only reduced in the chronic stress treatment (?23 %) due to reductions in spikelet fertility, grain number and grain weight. Symptom formation during the early growth stages did not reflect yield responses in all genotypes. Only one genotype showed increases in grain Fe concentrations (24 % in the acute stress and 44 % in the chronic stress) compared to the control.Conclusions
Contrasting genotypes responded differently to acute and chronic Fe toxicity, and one genotype showed consistent tolerance and the ability to translocate excess Fe into grains. These traits can be useful in the adaptive breeding of rice for Fe toxic environments.16.
Hansa Jain 《生物学前沿》2017,12(3):192-198
Background
Porphyromonas gingivalis is a periodontal pathogen, which is considered to be a keystone pathogen for periodontitis. A diverse conglomerate of P. gingivalis virulence factors including lipopolysaccharide, fimbriae, capsular polysaccharide, haemagglutinin and cysteine proteases (Arg-gingipains and Lys-gingipain) are considered to be involved in the pathogenesis of periodontitis. Leupeptin is a cysteine protease inhibitor which is specific for Arg gingipains. The present review focuses on action of leupeptin on Arg gingipains.Method
A search was carried out systematically from the start till September, 2016. The search was made in Medline database via PubMed. The keywords enlisted were “leupeptin”; “gingipains”; “periodontitis” using Boolean operator “and.”Results
The result was selection of 58 articles which linked leupeptin to periodontitis and gingipains; pathogenesis of periodontitis, pathogenicity of gingipains and role of leupeptin.Conclusion
It was concluded that leupeptin inhibits and attenuates a number of destructive activities of Arg gingipains including inhibition of platelet aggregation; inhibit degradation of LL-37, which is an antimicrobial peptide; blocking inhibition of monocyte chemoattractant protein; restoring level of interleukin-2; inhibiting degradation of collagen type I and IV to name a few.17.
Lenin D. Sarabia Berin A. Boughton Thusitha Rupasinghe Allison M. L. van de Meene Damien L. Callahan Camilla B. Hill Ute Roessner 《Metabolomics : Official journal of the Metabolomic Society》2018,14(5):63
Introduction
Mass spectrometry imaging (MSI) is a technology that enables the visualization of the spatial distribution of hundreds to thousands of metabolites in the same tissue section simultaneously. Roots are below-ground plant organs that anchor plants to the soil, take up water and nutrients, and sense and respond to external stresses. Physiological responses to salinity are multifaceted and have predominantly been studied using whole plant tissues that cannot resolve plant salinity responses spatially.Objectives
This study aimed to use a comprehensive approach to study the spatial distribution and profiles of metabolites, and to quantify the changes in the elemental content in young developing barley seminal roots before and after salinity stress.Methods
Here, we used a combination of liquid chromatography–mass spectrometry (LC–MS), inductively coupled plasma mass spectrometry (ICP–MS), and matrix-assisted laser desorption/ionization (MALDI–MSI) platforms to profile and analyze the spatial distribution of ions, metabolites and lipids across three anatomically different barley root zones before and after a short-term salinity stress (150 mM NaCl).Results
We localized, visualized and discriminated compounds in fine detail along longitudinal root sections and compared ion, metabolite, and lipid composition before and after salt stress. Large changes in the phosphatidylcholine (PC) profiles were observed as a response to salt stress with PC 34:n showing an overall reduction in salt treated roots. ICP–MS analysis quantified changes in the elemental content of roots with increases of Na+ and decreases of K+ content.Conclusion
Our results established the suitability of combining three mass spectrometry platforms to analyze and map ionic and metabolic responses to salinity stress in plant roots and to elucidate tolerance mechanisms in response to abiotic stress, such as salinity stress.18.
19.
Yeonyee Oh Suzanne L. Robertson Jennifer Parker David C. Muddiman Ralph A. Dean 《Proteome science》2017,15(1):20
Background
Fungi are constantly exposed to nitrogen limiting environments, and thus the efficient regulation of nitrogen metabolism is essential for their survival, growth, development and pathogenicity. To understand how the rice blast pathogen Magnaporthe oryzae copes with limited nitrogen availability, a global proteome analysis under nitrogen supplemented and nitrogen starved conditions was completed.Methods
M. oryzae strain 70–15 was cultivated in liquid minimal media and transferred to media with nitrate or without a nitrogen source. Proteins were isolated and subjected to unfractionated gel-free based liquid chromatography-tandem mass spectrometry (LC-MS/MS). The subcellular localization and function of the identified proteins were predicted using bioinformatics tools.Results
A total of 5498 M. oryzae proteins were identified. Comparative analysis of protein expression showed 363 proteins and 266 proteins significantly induced or uniquely expressed under nitrogen starved or nitrogen supplemented conditions, respectively. A functional analysis of differentially expressed proteins revealed that during nitrogen starvation nitrogen catabolite repression, melanin biosynthesis, protein degradation and protein translation pathways underwent extensive alterations. In addition, nitrogen starvation induced accumulation of various extracellular proteins including small extracellular proteins consistent with observations of a link between nitrogen starvation and the development of pathogenicity in M. oryzae.Conclusion
The results from this study provide a comprehensive understanding of fungal responses to nitrogen availability.20.