scholarly journals The Aspergillus nidulansnucAEndoGHomologue Is Not Involved in Cell Death

2010 ◽  
Vol 10 (2) ◽  
pp. 276-283 ◽  
Author(s):  
Bárbara de Castro Pimentel Figueiredo ◽  
Patrícia Alves de Castro ◽  
Taísa Magnani Dinamarco ◽  
Maria Helena S. Goldman ◽  
Gustavo Henrique Goldman
Keyword(s):  
Cell Death ◽  
Aspergillus Nidulans ◽  
Dna Fragmentation ◽  
Filamentous Fungi ◽  
Large Scale ◽  
Apoptosis Induction ◽  
Content Type ◽  
Endonuclease G ◽  
First Time

ABSTRACTUpon apoptosis induction, translocation of mammalian mitochondrial endonuclease G (EndoG) to the nucleus coincides with large-scale DNA fragmentation. Here, we describe for the first time a homologue of EndoG in filamentous fungi by investigating if theAspergillus nidulanshomologue of the EndoG gene, namednucAEndoG, is being activated during farnesol-induced cell death. Our results suggest that NucA is not involved in cell death, but it plays a role in the DNA-damaging response inA. nidulans.

scholarly journals Transcriptomic, Protein-DNA Interaction, and Metabolomic Studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual Spores

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming-Yueh Wu ◽  
Matthew E. Mead ◽  
Mi-Kyung Lee ◽  
George F. Neuhaus ◽  
Donovon A. Adpressa ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Secondary Metabolism ◽  
Aspergillus Nidulans ◽  
Filamentous Fungi ◽  
Genetic Regulatory Networks ◽  
Asexual Development ◽  
Morphological Development ◽  
Vast Number ◽  
Content Type ◽  
Metabolic Remodeling

ABSTRACT In filamentous fungi, asexual development involves cellular differentiation and metabolic remodeling leading to the formation of intact asexual spores. The development of asexual spores (conidia) in Aspergillus is precisely coordinated by multiple transcription factors (TFs), including VosA, VelB, and WetA. Notably, these three TFs are essential for the structural and metabolic integrity, i.e., proper maturation, of conidia in the model fungus Aspergillus nidulans. To gain mechanistic insight into the complex regulatory and interdependent roles of these TFs in asexual sporogenesis, we carried out multi-omics studies on the transcriptome, protein-DNA interactions, and primary and secondary metabolism employing A. nidulans conidia. RNA sequencing and chromatin immunoprecipitation sequencing analyses have revealed that the three TFs directly or indirectly regulate the expression of genes associated with heterotrimeric G-protein signal transduction, mitogen-activated protein (MAP) kinases, spore wall formation and structural integrity, asexual development, and primary/secondary metabolism. In addition, metabolomics analyses of wild-type and individual mutant conidia indicate that these three TFs regulate a diverse array of primary metabolites, including those in the tricarboxylic acid (TCA) cycle, certain amino acids, and trehalose, and secondary metabolites such as sterigmatocystin, emericellamide, austinol, and dehydroaustinol. In summary, WetA, VosA, and VelB play interdependent, overlapping, and distinct roles in governing morphological development and primary/secondary metabolic remodeling in Aspergillus conidia, leading to the production of vital conidia suitable for fungal proliferation and dissemination. IMPORTANCE Filamentous fungi produce a vast number of asexual spores that act as efficient propagules. Due to their infectious and/or allergenic nature, fungal spores affect our daily life. Aspergillus species produce asexual spores called conidia; their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by multiple transcription factors (TFs). To understand the underlying global regulatory programs and cellular outcomes associated with conidium formation, genomic and metabolomic analyses were performed in the model fungus Aspergillus nidulans. Our results show that the fungus-specific WetA/VosA/VelB TFs govern the coordination of morphological and chemical developments during sporogenesis. The results of this study provide insights into the interdependent, overlapping, or distinct genetic regulatory networks necessary to produce intact asexual spores. The findings are relevant for other Aspergillus species such as the major human pathogen Aspergillus fumigatus and the aflatoxin producer Aspergillus flavus.

scholarly journals Protective effect of zinc-N-acetylcysteine on the rat kidney during cold storage

2013 ◽  
Vol 305 (7) ◽  
pp. F1022-F1030 ◽  
Author(s):  
Mandeep Singh ◽  
Dolapo T. Odeniyi ◽  
Eugene O. Apostolov ◽  
Alena Savenka ◽  
Todd Fite ◽  
...  
Keyword(s):  
Cell Death ◽  
Dna Fragmentation ◽  
Cold Storage ◽  
Ex Vivo ◽  
Rat Kidney ◽  
Maximum Effect ◽  
Kidney Preservation ◽  
Endonuclease G ◽  
Normal Rat ◽  
Rat Kidneys

Cold storage of kidneys before transplantation is problematic because of the limited survival time of the allografts. In this study, zinc- N-acetylcysteine (ZnNAC) was shown to be a potent endonuclease inhibitor and antioxidant, and it was tested as a potential additive to a cold storage solution for kidney preservation. Exposure of normal rat kidney NRK-52E cells to ZnNAC resulted in zinc delivery to the cells as determined by TFL-Zn fluorophore and partial protection of the cells against injury by cold storage in University of Wisconsin solution (UWS) as measured by propidium iodide assay. Ex vivo, rat kidneys demonstrated time- and temperature-dependent DNA fragmentation as assessed by TUNEL assay, indicating irreversible cell death. DNA fragmentation was faster in the medulla than in the cortex, and tubules were affected more than glomeruli. Perfusion of rat kidneys with cold ZnNAC solution in UWS significantly inhibited cell death both in the cortex and medulla at concentrations of 0.3–30 mM compared with UWS alone, with a maximum effect at 1–10 mM ZnNAC. Cold storage of the kidney significantly increased quantities of cleaved caspase-3 and endonuclease G (EndoG) in the tissue, which were abolished by 10 mM ZnNAC, indicating its ability to suppress both caspase-dependent and -independent cell death. Therefore, supplementation of UWS with ZnNAC can decrease DNA fragmentation and protect kidney allografts from cell death due to cold storage.

Conflict resolution practice in public procurement: evidence from Russia

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Yuliya Rodionova
Keyword(s):  
Conflict Resolution ◽  
Large Scale ◽  
Public Procurement ◽  
Content Type ◽  
Conflict Situations ◽  
Judicial Proceedings ◽  
Survey Results ◽  
Conflict Handling ◽  
Informal Relations ◽  
First Time

Purpose This paper aims to analyze conflict resolution practice in public procurement. The specific feature of this sphere is the presence of the state and the resulting differences in assessing the chances of protecting one’s interests in court, as well as the effectiveness of judicial conflict resolution mechanisms. Design/methodology/approach This paper is based on the findings of a large-scale survey of suppliers conducted in 2017. To identify the characteristics of suppliers that use different conflict resolution mechanisms, probit-models were evaluated. For robustness check, combined mechanisms for resolving conflict situations were also considered and multi-nomial logistic regression was used. Findings The survey results showed that the majority of suppliers prefer to resolve conflicts in public procurement using an out-of-court negotiation with procurers while only 31% of respondents resort to judicial proceedings. At the same time, suppliers potentially involved in informal relations with procurers, are less likely to go to court and less often use negotiations. Practical implications The results of the study can be used as a justification for the development of a regulatory and organizational framework for the use of negotiations, mediation, arbitration and other alternate methods of conflict resolution in public procurement. Originality/value This paper makes an important contribution to the conflict-handling strategies of businesses and government by presenting for the first time a quantitative assessment of the prevalence of mechanisms for resolving conflicts in public procurement and factors influencing the choice of a conflict resolution mechanism.

scholarly journals Disuccinyl Betulin Triggers Metacaspase-Dependent Endonuclease G-Mediated Cell Death in Unicellular Protozoan Parasite Leishmania donovani

2014 ◽  
Vol 58 (4) ◽  
pp. 2186-2201 ◽  
Author(s):  
Sayan Chowdhury ◽  
Tulika Mukherjee ◽  
Somenath Roy Chowdhury ◽  
Souvik Sengupta ◽  
Sibabrata Mukhopadhyay ◽  
...  
Keyword(s):  
Cell Death ◽  
Leishmania Donovani ◽  
Protozoan Parasite ◽  
Degradation Process ◽  
Dna Lesions ◽  
Death Process ◽  
Unicellular Organism ◽  
Content Type ◽  
Atp Production ◽  
Endonuclease G

ABSTRACTThe unicellular organismLeishmaniaundergoes apoptosis-like cell death in response to external stress or exposure to antileishmanial agents. Here, we showed that 3-O,28-O-disuccinyl betulin (DiSB), a potent topoisomerase type IB inhibitor, induced parasitic cell death by generating oxidative stress. The characteristic feature of the death process resembled the programmed cell death (PCD) seen in higher eukaryotes. In the current study, the generation of reactive oxygen species (ROS), followed by the depolarization of mitochondrial membrane potential (ΔΨm), caused a loss in ATP production inLeishmaniaparasites. This further gave positive feedback to produce a large amount of ROS, which in turn caused oxidative DNA lesions and genomic DNA fragmentation. The treatment of promastigotes with DiSB induced high expression levels of metacaspase protein that led to cell death in this unicellular organism. The PCD was insensitive to benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), suggesting that the death process was not associated with the activation of caspases. DiSB treatment translocatedLeishmania donovaniendonuclease G (LdEndoG) from mitochondria to the nucleus, which was responsible for the DNA degradation process. Conditional antisense knockdown ofL. donovanimetacaspase (LdMC), as well as EndoG, -subverted death of the parasite and rescued cell cycle arrest in G1phase. The present study on the effector molecules associated with the PCD pathway of the parasite should help to manifest the mechanisms of PCD and also might be exploited in antileishmanial chemotherapy.

Environment and technology dominate the WEF agenda

2017 ◽  
Keyword(s):  
Climate Change ◽  
Large Scale ◽  
The United States ◽  
Extreme Weather Events ◽  
Content Type ◽  
Mitigation And Adaptation ◽  
The People ◽  
Impact Risk ◽  
Trade Deals ◽  
First Time

Significance For the first time in the eleven-year history of the survey, no economic risk makes the list of the top five most likely or biggest impact risks. In contrast, large-scale terrorist attacks make the top five most likely risks for the first time and weapons of mass destruction are cited as the highest impact risk. All five environment-related risks are ranked among the top ten highest impact risks for the first time -- four in the top five: extreme weather events; water crises; major natural disasters; and failure of climate change mitigation and adaptation. The survey cites strengthening global cooperation systems as a top five challenge, and says these environmental risks will be exacerbated if cooperation diminishes. Impacts Nearly a third of respondents think that increasing polarisation will be an underlying trend over the next ten years. More must be done to include the people left behind by technological change -- more than 4 billion lack internet access. The United States may withdraw from the Paris climate change agreement, and a number of free trade deals are at risk.

scholarly journals Functional Analysis of Sterol Transporter Orthologues in the Filamentous Fungus Aspergillus nidulans

2015 ◽  
Vol 14 (9) ◽  
pp. 908-921 ◽  
Author(s):  
Nicole Bühler ◽  
Daisuke Hagiwara ◽  
Norio Takeshita
Keyword(s):  
Plasma Membrane ◽  
Aspergillus Nidulans ◽  
Filamentous Fungi ◽  
Gene Deletion ◽  
Fluorescent Protein ◽  
Fungal Growth ◽  
Hyphal Growth ◽  
Apical Plasma Membrane ◽  
Important Species ◽  
Content Type

ABSTRACT Polarized growth in filamentous fungi needs a continuous supply of proteins and lipids to the growing hyphal tip. One of the important membrane compounds in fungi is ergosterol. At the apical plasma membrane ergosterol accumulations, which are called sterol-rich plasma membrane domains (SRDs). The exact roles and formation mechanism of the SRDs remained unclear, although the importance has been recognized for hyphal growth. Transport of ergosterol to hyphal tips is thought to be important for the organization of the SRDs. Oxysterol binding proteins, which are conserved from yeast to human, are involved in nonvesicular sterol transport. In Saccharomyces cerevisiae seven oxysterol-binding protein homologues (OSH1 to -7) play a role in ergosterol distribution between closely located membranes independent of vesicle transport. We found five homologous genes ( oshA to oshE ) in the filamentous fungi Aspergillus nidulans . The functions of OshA-E were characterized by gene deletion and subcellular localization. Each gene-deletion strain showed characteristic phenotypes and different sensitivities to ergosterol-associated drugs. Green fluorescent protein-tagged Osh proteins showed specific localization in the late Golgi compartments, puncta associated with the endoplasmic reticulum, or diffusely in the cytoplasm. The genes expression and regulation were investigated in a medically important species Aspergillus fumigatus , as well as A. nidulans . Our results suggest that each Osh protein plays a role in ergosterol distribution at distinct sites and contributes to proper fungal growth.

scholarly journals Partial Prion Cross-Seeding between Fungal and Mammalian Amyloid Signaling Motifs

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Thierry Bardin ◽  
Asen Daskalov ◽  
Sophie Barrouilhet ◽  
Alexandra Granger-Farbos ◽  
Bénédicte Salin ◽  
...  
Keyword(s):  
Cell Death ◽  
Filamentous Fungi ◽  
Sequence Similarity ◽  
Podospora Anserina ◽  
Content Type ◽  
Cell Death Pathways ◽  
Prion Propagation ◽  
Signaling Modules ◽  
Β Sheet

ABSTRACT In filamentous fungi, NLR-based signalosomes activate downstream membrane-targeting cell death-inducing proteins by a mechanism of amyloid templating. In the species Podospora anserina, two such signalosomes, NWD2/HET-S and FNT1/HELLF, have been described. An analogous system involving a distinct amyloid signaling motif, termed PP, was also identified in the genome of the species Chaetomium globosum and studied using heterologous expression in Podospora anserina. The PP motif bears resemblance to the RIP homotypic interaction motif (RHIM) and to RHIM-like motifs controlling necroptosis in mammals and innate immunity in flies. We identify here a third NLR signalosome in Podospora anserina comprising a PP motif and organized as a two-gene cluster encoding an NLR and an HELL domain cell death execution protein termed HELLP. We show that the PP motif region of HELLP forms a prion we term [π] and that [π] prions trigger the cell death-inducing activity of full-length HELLP. We detect no prion cross-seeding between HET-S, HELLF, and HELLP amyloid motifs. In addition, we find that, like PP motifs, RHIMs from human RIP1 and RIP3 kinases are able to form prions in Podospora and that [π] and [Rhim] prions partially cross-seed. Our study shows that Podospora anserina displays three independent cell death-inducing amyloid signalosomes. Based on the described functional similarity between RHIM and PP, it appears likely that these amyloid motifs constitute evolutionarily related cell death signaling modules. IMPORTANCE Amyloids are β-sheet-rich protein polymers that can be pathological or display a variety of biological roles. In filamentous fungi, specific immune receptors activate programmed cell death execution proteins through a process of amyloid templating akin to prion propagation. Among these fungal amyloid signaling sequences, the PP motif stands out because it shows similarity to the RHIM, an amyloid sequence controlling necroptotic cell death in mammals. We characterized an amyloid signaling system comprising a PP motif in the model species Podospora anserina, thus bringing to three the number of independent amyloid signaling cell death pathways described in that species. We then showed that human RHIMs not only propagate as prions in P. anserina but also partially cross-seed with fungal PP prions. These results indicate that, in addition to showing sequence similarity, the PP and RHIM motifs are at least partially functionally related, supporting a model of long-term evolutionary conservation of amyloid signaling mechanisms from fungi to mammals.

scholarly journals Right-first-time dyeing: a design of experiments approach for the optimisation of dyeing-processes using hard water

2019 ◽  
Vol 48 (5) ◽  
pp. 449-455
Author(s):  
Saira Faisal ◽  
Aurelio Tronci ◽  
Muhammad Ali ◽  
Erum Bashir ◽  
Long Lin
Keyword(s):  
Predictive Models ◽  
Textile Industry ◽  
Large Scale ◽  
Mineral Content ◽  
Water Hardness ◽  
Hard Water ◽  
Coefficient Of Determination ◽  
Content Type ◽  
Independent Variables ◽  
First Time

Purpose The purpose of this study was to optimise the dyeing conditions to achieve right-first-time dyeing in hard water. Owing to the persistent water scarcity for more than two decades now, the textile industry in Pakistan is forced to rely on high-mineral-content ground water for use in textile wet processing. Furthermore, the limited amount of municipal water that is at the disposal of the textile industry is also high in mineral content. Thus, on the large scale, water hardness has become an acute problem for the textile processor. In particular, in the dyeing process, water hardness is known to have crucial effects. However, to-date, no systematic study has been conducted on this aspect of textile dyeing. Design/methodology/approach In this study, 32 full factorial design was used to optimise the dyeing conditions to achieve right-first-time dyeing in hard water. Thus, cotton fabric was dyed with Red Reactive dye (of dyebath concentration at 5, 10 and 15 g/L) in prepared hard water (of hardness at 10, 40 and 70°dH), respectively. Analysis of variance, coefficient of determination (R2) and p-values for the models were used to evaluate the adequacy of the predictive models. The surface plots of the effects were studied to further examine the interactions of two independent variables. Derringer’s desirability function was used to determine the optimum levels of each variable. Findings Three levels for both independent variables generate second-order polynomial models to predict the colour strength, lightness, red/green, yellow/blue and total colour difference values of dyed cotton. The obtained predictive models point out the considerable influence of both water hardness and dye concentration on right-first-time dyeing. Originality/value Such a finding enabled the dye-mill to produce the correct shade at water hardness of 10°dH and 15 g/L dye concentration, without the need for corrective reprocessing.

scholarly journals Induction of Apoptosis by Sphingoid Long-Chain Bases in Aspergillus nidulans

2003 ◽  
Vol 23 (1) ◽  
pp. 163-177 ◽  
Author(s):  
Jijun Cheng ◽  
Tae-Sik Park ◽  
Li-Chun Chio ◽  
Anthony S. Fischl ◽  
Xiang S. Ye
Keyword(s):  
Aspergillus Nidulans ◽  
Dna Fragmentation ◽  
Large Scale ◽  
Spin Trap ◽  
Sphingolipid Metabolism ◽  
Ideal Model ◽  
Naturally Occurring ◽  
Rapid Accumulation ◽  
Ideal Model System ◽  
Induction Of Apoptosis

ABSTRACT Sphingolipid metabolism is implicated to play an important role in apoptosis. Here we show that dihydrosphingosine (DHS) and phytosphingosine (PHS), two major sphingoid bases of fungi, have potent fungicidal activity with remarkably high structural and stereochemical specificity against Aspergillus nidulans. In fact, only naturally occurring DHS and PHS are active. Further analysis revealed that DHS and PHS induce rapid DNA condensation independent of mitosis, large-scale DNA fragmentation, and exposure of phosphatidylserine, all common morphological features characteristic of apoptosis, suggesting that DHS and PHS induce apoptosis in A. nidulans. The finding that DNA fragmentation requires protein synthesis, which implies that an active process is involved, further supports this proposition. The induction of apoptosis by DHS and PHS is associated with the rapid accumulation of reactive oxygen species (ROS). However, ROS are not required for apoptosis induced by DHS and PHS, as scavenging of ROS by a free radical spin trap has no effect. We further demonstrate that apoptosis induced by DHS and PHS is independent of metacaspase function but requires mitochondrial function. Together, the results suggest that DHS and PHS induce a type of apoptosis in A. nidulans most similar to the caspase-independent apoptosis observed in mammalian systems. As A. nidulans is genetically tractable, this organism should be an ideal model system for dissecting sphingolipid signaling in apoptosis and, importantly, for further elucidating the molecular basis of caspase-independent apoptosis.

scholarly journals Amoebicidal Activity of Caffeine and Maslinic Acid by the Induction of Programmed Cell Death in Acanthamoeba

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Carmen M. Martín-Navarro ◽  
Atteneri López-Arencibia ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
Emilie Fouque ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Glycogen Phosphorylase ◽  
Extracellular Proteases ◽  
Free Living ◽  
Maslinic Acid ◽  
Content Type ◽  
Granulomatous Amoebic Encephalitis ◽  
First Time ◽  
Amoebicidal Activity

ABSTRACT Free-living amoebae of the genus Acanthamoeba are the causal agents of a sight-threatening ulceration of the cornea called Acanthamoeba keratitis, as well as the rare but usually fatal disease granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba infections, they are generally lengthy and/or have limited efficacy. For the best clinical outcome, treatments should target both the trophozoite and the cyst stages, as cysts are known to confer resistance to treatment. In this study, we document the activities of caffeine and maslinic acid against both the trophozoite and the cyst stages of three clinical strains of Acanthamoeba. These drugs were chosen because they are reported to inhibit glycogen phosphorylase, which is required for encystation. Maslinic acid is also reported to be an inhibitor of extracellular proteases, which may be relevant since the protease activities of Acanthamoeba species are correlated with their pathogenicity. We also provide evidence for the first time that both drugs exert their anti-amoebal effects through programmed cell death.

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