Mechanistic concepts of iron-sulfur protein biogenesis in Biology Braymer, Joseph J.; Freibert, Sven A.; Rakwalska-Bange, Magdalena ...
Biochimica et biophysica acta. Molecular cell research,
January 2021, 2021-01-00, 20210101, Letnik:
1868, Številka:
1
Journal Article
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Iron-sulfur (Fe/S) proteins are present in virtually all living organisms and are involved in numerous cellular processes such as respiration, photosynthesis, metabolic reactions, nitrogen fixation, ...radical biochemistry, protein synthesis, antiviral defense, and genome maintenance. Their versatile functions may go back to the proposed role of their Fe/S cofactors in the origin of life as efficient catalysts and electron carriers. More than two decades ago, it was discovered that the in vivo synthesis of cellular Fe/S clusters and their integration into polypeptide chains requires assistance by complex proteinaceous machineries, despite the fact that Fe/S proteins can be assembled chemically in vitro. In prokaryotes, three Fe/S protein biogenesis systems are known; ISC, SUF, and the more specialized NIF. The former two systems have been transferred by endosymbiosis from bacteria to mitochondria and plastids, respectively, of eukaryotes. In their cytosol, eukaryotes use the CIA machinery for the biogenesis of cytosolic and nuclear Fe/S proteins. Despite the structural diversity of the protein constituents of these four machineries, general mechanistic concepts underlie the complex process of Fe/S protein biogenesis. This review provides a comprehensive and comparative overview of the various known biogenesis systems in Biology, and summarizes their common or diverging molecular mechanisms, thereby illustrating both the conservation and diverse adaptions of these four machineries during evolution and under different lifestyles. Knowledge of these fundamental biochemical pathways is not only of basic scientific interest, but is important for the understanding of human ‘Fe/S diseases’ and can be used in biotechnology.
•FeS proteins assist numerous cellular processes and many are essential for life.•FeS proteins are assembled by one or more out of four different machineries.•Similar mechanistic concepts underlie FeS protein biogenesis in all machineries.•Biogenesis involves synthesis, trafficking and apoprotein targeting of FeS clusters.•Minimal machineries reveal the basic biochemical requirements for biogenesis.
The ontogeny of macrophages in most organ/tissues in human body has been proven. Due to the limited number and inaccessibility of synovial macrophages (SM), the origin of SM has not been fully ...illuminated. The objective of this study was designed to investigate the ontogeny of SM and to evaluate the role of SM from different origins in arthritis. Two origins of SM, embryonic SM (ESM) and bone marrow SM (BMSM) were identified in Cx3cr1-EGFP mice, CCR2
mice and bone marrow (BM) chimera model by using a stringent sorting strategy. The cellular features, including dynamic total cell number,
proliferation, phagocytosis and expressions of pro-inflammatory and anti-inflammatory genes, of ESM and BMSM were compared. In addition, ESM and BMSM showed different expression patterns in Rheumatoid Arthritis (RA) patients' synovium and during the developmental process of collagen-induced arthritis (CIA) mice. Taken together, these results demonstrated that the SM at least has two origins, ESM and BMSM. The different cellular property and dynamic expression patterns in RA patients/CIA mice highlight the notion that ESM and BMSM might play different role in arthritis.
Leishmania donovani is the causative unicellular parasite for visceral leishmaniasis (VL); and FeS proteins are likely to be very essential for their survival and viability. Cytosolic FeS cluster ...assembly (CIA) machinery is one of the four systems for the biosynthesis and transfer of FeS clusters among eukaryotes; Cfd1 and Nbp35 are the scaffold components for cytosolic FeS cluster biogenesis. We investigated the role of CIA machinery components and purified Cfd1 and Nbp35 proteins of L. donovani. We also investigated the interactive nature between LdCfd1 and LdNbp35 proteins by in silico analysis, in vitro co-purification, pull down assays along with in vivo immuno-precipitation; which inferred that both LdCfd1 and LdNbp35 proteins are interacting with each other. Thus, our collective data revealed the interaction between these two proteins which forms a stable complex that can be attributed to the cellular process of FeS clusters biogenesis, and transfer to target apo-proteins of L. donovani. The expression of Cfd1 and Nbp35 proteins in Amp B resistant parasites is up-regulated leading to increased amount of FeS proteins. Hence, it favors increased tolerance towards ROS level, which helps parasites survival under drug pressure contributing in Amphotericin B resistance.
Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease. Its high disability rate has a serious impact on society and individuals, but there is still a lack of effective and reliable ...diagnostic markers and therapeutic targets for RA. In this study, we integrated RA patient information from three GEO databases for differential gene expression analysis. Additionally, we also obtained pan-cancer-related genes from the TCGA and GTEx databases. For RA-related differential genes, we performed functional enrichment analysis and constructed a weighted gene co-expression network (WGCNA). Then, we obtained 490 key genes by intersecting the significant module genes selected by WGCNA and the differential genes. After using the RanddomForest, SVM-REF, and LASSO three algorithms to analyze these key genes and take the intersection, based on the four core genes (BTN3A2, CYFIP2, ST8SIA1, and TYMS) that we found, we constructed an RA diagnosis. The nomogram model showed good reliability and validity after evaluation, and the ROC curves of the four genes showed that these four genes played an important role in the pathogenesis of RA. After further gene correlation analysis, immune infiltration analysis, and mouse gene expression validation, we finally selected CYFIP2 as the cut-in gene for pan-cancer analysis. The results of the pan-cancer analysis showed that CYFIP2 was closely related to the prognosis of patients with various tumors, the degree of immune cell infiltration, as well as TMB, MSI, and other indicators, suggesting that this gene may be a potential intervention target for human diseases including RA and tumors.
Giant cell arteritis (GCA) is a granulomatous systemic vasculitis of large- and medium-sized arteries that affects the elderly. In recent years, advances in diagnostic imaging have revealed a greater ...degree of large vessel involvement than previously recognized, distinguishing classical cranial- from large vessel (LV)- GCA. GCA often co-occurs with the poorly understood inflammatory arthritis/bursitis condition polymyalgia rheumatica (PMR) and has overlapping features with other non-infectious granulomatous vasculitides that affect the aorta, namely Takayasu Arteritis (TAK) and the more recently described clinically isolated aortitis (CIA). Here, we review the literature focused on the immunopathology of GCA on the background of the three settings in which comparisons are informative: LV and cranial variants of GCA; PMR and GCA; the three granulomatous vasculitides (GCA, TAK, and CIA). We discuss overlapping and unique features between these conditions across clinical presentation, epidemiology, imaging, and conventional histology. We propose a model of GCA where abnormally activated circulating cells, especially monocytes and CD4
T cells, enter arteries after an unknown stimulus and cooperate to destroy it and review the evidence for how this mechanistically occurs in active disease and improves with treatment.
PurposeThis paper discusses how the features of blockchain technology impact supply chain transparency through the lens of the information security triad (confidentiality, integrity and ...availability). Ultimately, propositions are developed to encourage future research in supply chain applications of blockchain technology.Design/methodology/approachPropositions are developed based on a synthesis of the information security and supply chain transparency literature. Findings from text mining of Twitter data and a discussion of three major blockchain use cases support the development of the propositions.FindingsThe authors note that confidentiality limits supply chain transparency, which causes tension between transparency and security. Integrity and availability promote supply chain transparency. Blockchain features can preserve security and increase transparency at the same time, despite the tension between confidentiality and transparency.Research limitations/implicationsThe research was conducted at a time when most blockchain applications were still in pilot stages. The propositions developed should therefore be revisited as blockchain applications become more widely adopted and mature.Originality/valueThis study is among the first to examine the way blockchain technology eases the tension between supply chain transparency and security. Unlike other studies that have suggested only positive impacts of blockchain technology on transparency, this study demonstrates that blockchain features can influence transparency both positively and negatively.
Computer networks are built to achieve the main goal of communicating with each other . During the transmission process, it is expected that information can be conveyed quickly, efficiently and ...safely. Network security serves to avoid damage or even data loss caused by attacker activities during the communication process. Security aspects that need to be maintained in data information are Confidentiality, Integrity and Availability. Intrusion Prevention System is a solution that can maintain network security from various attacks. The Intrusion Prevention System will act as a protector on the network by detecting and preventing suspicious traffic on nodes in a network. The Intrusion Prevention System in its implementation has several tools which are used in this study, namely Snort and IPTables. Testing is done by performing attacks on the Web Server. The attacks carried out are Port Scanning, DDoS attacks and Brute Force. The results of this study are based on the CIA Triad with the three attacks having different characteristics in terms of cause and effect. On the defense side, Port Scanning and Brute Force can be easily prevented by IPS, but in DDoS attacks there are differences in results between drop and reject rule. In a DDoS attack with an action drop rule, it can recover the web server in 160 seconds while the action reject rule can be restored at 145 seconds which normally can be recovered in a DDoS attack in 165 seconds. The IPS server can also reduce resources when there is a DDoS attack by 9.2% .
Background and Purpose
Short‐chain fatty acids (SCFAs) are metabolites from gut microbes involved in the host's inflammatory response and immunity. The aim of this study was to investigate the role ...of SCFAs in rheumatoid arthritis (RA) and possible mechanisms.
Experimental Approach
Gut microbiota diversity in mice was analysed by 16S rDNA sequencing. SCFAs levels were analysed by gas chromatography mass spectrometry. T and B cells were analysed by flow cytometry. Bone damage was analysed by micro‐CT and X‐ray. Histopathological status was analysed by HE staining. Proteins in tissues were analysed by immunohistochemistry and PCR. Mice with CD19+ B cells deficient in FFA2 receptors were used to explore the molecular mechanisms involved.
Key Results
Levels of acetate, propionate, butyrate, and valerate were decreased in RA patients, and the first three correlated positively with the frequency of Bregs but not Tregs in peripheral blood. Administration of the three SCFAs prior to the onset of collagen‐induced arthritis in mice improved arthritic symptoms, increased the Bregs frequency, and decreased transitional B and follicular B cell frequency. However, the preceding phenomena could not be observed in mice with CD19+ B cells deficient in FFA2 receptors. The effects of the three SCFAs in RA were dependent on FFA2 receptors but were independent of the other five B cell receptors (FFA3 receptor, HCA2 receptor, PPARγ, Olfr‐78, and AhR).
Conclusions and Implications
SCFAs regulate B cells differentiation via FFA2 receptors to alleviate RA. This provides new insights into the treatment of RA from an immunological and microbiological perspective.
Gut microbial‐derived short‐chain fatty acids (SCFAs) regulate B cell differentiation via the FFA2 receptor to reduce bone erosion and inflammatory responses in rheumatoid arthritis.
Astragalin, as a bioactive flavonoid with anti-inflammatory, antioxidant, and protective properties, provides a potential agent for rheumatoid arthritis (RA). In this study, its therapeutic efficacy ...and the underlying mechanisms were explored using DBA/1J mice with collagen-induced arthritis (CIA). It was demonstrated that astragalin could significantly attenuate inflammation of CIA mice. The effects were associated with decreased severity of arthritis (based on the arthritis index), joint swelling and reduced bone erosion and destruction. Furthermore, astragalin treatment suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), and inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) in chondrocytes and synovial cells of CIA mice. Fibroblast-like synoviocytes derived from RA patients (MH7A cells) were applied to verify these effects.
, astragalin inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) dose-dependently in TNF-α-induced MH7A cells, with no apparent cytotoxicity. Furthermore, astragalin suppressed the phosphorylation of p38, JNK, and the activation of c-Jun/AP-1 in TNF-α-induced MH7A cells. In conclusion, it has proven that astragalin could attenuate synovial inflammation and joint destruction in RA at least partially by restraining the phosphorylation of MAPKs and the activating of c-Jun/AP-1. Therefore, astragalin can be a potential therapeutic agent for RA.
Delta wetland sediments constitute a long-term natural carbon sink and play a critical role in the global carbon cycle. In this study, borehole core ZK3 (36.7-m long), drilled in 2012 in the Liaohe ...Delta wetland, was investigated to assess the rate of carbon sequestration and the factors influencing carbon burial since the Late Pleistocene. Here we report the results of integrated analyses of the core, including its sedimentary lithology, grain size, foraminiferal abundance, chemical elements, and accelerator mass spectrometry (AMS)14C and optically stimulated luminescence (OSL) dates. The sedimentary environment has evolved from a fluvial-deposit, limnetic-deposit, littoral-deposit, shallow sea–deposit, and finally to a delta-deposit environment since 40,000 cal yr BP. Environmentally induced differences in apparent mass accumulation rates (AMARs) of organic carbon (OC) have been significant; they have ranged between 3.73 and 30.77 g/(m2·yr). The fact that the highest rates were associated with the delta-deposit environment indicates that the rate of carbon sequestration was greater in the sediments of estuarine wetlands than sediments of the continental shelf. The chemical index of alteration (CIA) proxy responded to several cold events, and there was a positive correlation between the CIA and OC-AMAR. Climate may therefore have regulated the excursions of ecosystem productions and in turn impacted the dynamics of carbon burial.
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