Mechanism and stability of type II bacterial toxin‐antitoxin complexes and the role of regulated antitoxin proteolysis that releases toxin

Type II bacterial toxin-antitoxin (TA) systems are found in most bacteria, archaea, and mobile genetic elements. TAs are usually found as a bi-cistronic operon composed of an unstable antitoxin and a stable toxin that targets crucial cellular functions like DNA supercoiling, cell-wall synthesis or mRNA translation. The type II RelBE system encoded by the pathogen Streptococcus pneumoniae is highly conserved among different strains and participates in biofilm formation and response to oxidative stress. Here, we have analyzed the participation of the RelB antitoxin and the RelB:RelE protein complex in the self-regulation of the pneumococcal relBE operon. RelB acted as a weak repressor, whereas RelE performed the role of a co-repressor. By DNA footprinting experiments, we show that the proteins bind to a region that encompasses two palindromic sequences that are located around the −10 sequences of the single promoter that directs the synthesis of the relBE mRNA. High-resolution footprinting assays showed the distribution of bases whose deoxyriboses are protected by the bound proteins, demonstrating that RelB and RelB:RelE contacted the DNA backbone on one face of the DNA helix and that these interactions extended beyond the palindromic sequences. Our findings suggest that the binding of the RelBE proteins to its DNA target would lead to direct inhibition of the binding of the host RNA polymerase to the relBE promoter.

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The Role of NKT Cells in Glioblastoma

Cells ◽

10.3390/cells10071641 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1641

Author(s):

Emily E. S. Brettschneider ◽

Masaki Terabe

Keyword(s):

Immune Responses ◽

Cell Activity ◽

Nkt Cells ◽

Type I ◽

Type Ii ◽

Central Nervous System Diseases ◽

Nkt Cell ◽

Lipid Antigens ◽

Immunoregulatory Mechanisms

Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.

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Dark matter candidates in a type-II radiative neutrino mass model

Journal of High Energy Physics ◽

10.1007/jhep06(2021)072 ◽

2021 ◽

Vol 2021 (6) ◽

Author(s):

Roberto A. Lineros ◽

Mathias Pierre

Keyword(s):

Dark Matter ◽

Neutral Particle ◽

Matter Density ◽

Indirect Detection ◽

Dark Matter Candidate ◽

Neutrino Masses ◽

Type Ii ◽

Mass Model ◽

Direct And Indirect Detection

Abstract We explore the connection between Dark Matter and neutrinos in a model inspired by radiative Type-II seessaw and scotogenic scenarios. In our model, we introduce new electroweakly charged states (scalars and a vector-like fermion) and impose a discrete ℤ2 symmetry. Neutrino masses are generated at the loop level and the lightest ℤ2-odd neutral particle is stable and it can play the role of a Dark Matter candidate. We perform a numerical analysis of the model showing that neutrino masses and flavour structure can be reproduced in addition to the correct dark matter density, with viable DM masses from 700 GeV to 30 TeV. We explore direct and indirect detection signatures and show interesting detection prospects by CTA, Darwin and KM3Net and highlight the complementarity between these observables.

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The Properties and Role of O-Acyl-ω-hydroxy Fatty Acids and Type I-St and Type II Diesters in the Tear Film Lipid Layer Revealed by a Combined Chemistry and Biophysics Approach

The Journal of Organic Chemistry ◽

10.1021/acs.joc.0c02882 ◽

2021 ◽

Author(s):

Tuomo Viitaja ◽

Jan-Erik Raitanen ◽

Jukka Moilanen ◽

Riku O. Paananen ◽

Filip S. Ekholm

Keyword(s):

Fatty Acids ◽

Tear Film ◽

Hydroxy Fatty Acids ◽

Type I ◽

Type Ii ◽

Lipid Layer

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RegulatING chromatin regulators: post-translational modification of the ING family of epigenetic regulators

Biochemical Journal ◽

10.1042/bj20121632 ◽

2013 ◽

Vol 450 (3) ◽

pp. 433-442 ◽

Cited By ~ 8

Author(s):

Shankha Satpathy ◽

Arash Nabbi ◽

Karl Riabowol

Keyword(s):

Biological Significance ◽

Type Ii ◽

Post Translational Modification ◽

Post Translational Modifications ◽

Chromatin Regulators ◽

Cancer Types ◽

Splicing Isoforms ◽

Enrichment Techniques ◽

Affect Cell Growth

The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of PTMs (post-translational modifications) of INGs is important in understanding how ING functions are fine-tuned in the physiological setting and how they add to the repertoire of activities affected by the INGs. In the present paper we review the different PTMs that have been reported to occur on INGs. We discuss the PTMs that modulate ING function under normal conditions and in response to a variety of stresses. We also describe the ING PTMs that have been identified by several unbiased MS-based PTM enrichment techniques and subsequent proteomic analysis. Among the ING PTMs identified to date, a subset has been characterized for their biological significance and have been shown to affect processes including subcellular localization, interaction with enzymatic complexes and ING protein half-life. The present review aims to highlight the emerging role of PTMs in regulating ING function and to suggest additional pathways and functions where PTMs may effect ING function.

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Native Gold in the Chudnoe Au-Pd-REE Deposit (Subpolar Urals, Russia): Composition, Minerals in Intergrowth and Genesis

Minerals ◽

10.3390/min11050451 ◽

2021 ◽

Vol 11 (5) ◽

pp. 451

Author(s):

Galina Palyanova ◽

Valery Murzin ◽

Andrey Borovikov ◽

Nikolay Karmanov ◽

Sergei Kuznetsov

Keyword(s):

Native Gold ◽

Microprobe Analysis ◽

Electron Microprobe Analysis ◽

Gold Mineralization ◽

Type I ◽

Type Ii ◽

Subpolar Urals ◽

Type V ◽

Impurity Elements

Composition of native gold and minerals in intergrowth with rhyolites of the Chudnoe Au-Pd-REE deposit (Subpolar Urals, Russia) was studied using optical microscopy, scanning electron microscopy, and electron microprobe analysis. Five varieties of native gold have been identified, based on the set of impurity elements and their quantities, and on intergrown minerals. Native gold in rhyolites from the Ludnaya ore zone is homogeneous and contains only Ag (fineness 720‰, type I). It is in intergrowth with fuchsite or allanite and mertieite-II. In rhyolites from the Slavnaya ore zone, native gold is heterogeneous, has a higher fineness, different sets and contents of elements: Ag, Cu, 840–860‰ (type II); Ag, Cu, Pd, 830–890‰ (III); Ag, Pd, Cu, Hg, 840–870‰ (IV). It occurs in intergrowth with fuchsite, albite, and mertieite-II (type II), or albite, quartz, and atheneite (III), or quartz, albite, K-feldspar, and mertieite-II (IV). High fineness gold (930–1000‰, type V) with low contents of Ag, Cu, and Pd or their absence occurs in the form as microveins, fringes and microinclusions in native gold II–IV. Tetra-auricupride (AuCu) is presented as isometric inclusions in gold II and platelets in the decay structures in gold III and IV. The preliminary data of a fluid inclusions study showed that gold mineralization at the Chudnoe deposit could have been formed by chloride fluids of low and medium salinity at temperatures from 105 to 230 °C and pressures from 5 to 115 MPa. The formation of native gold I is probably related to fuchsitization and allanitization of rhyolites. The formation of native gold II-V is also associated with the same processes, but it is more complicated and occurred later with a significant role of Na-, Si-, and K-metasomatism. The presence of Pd and Cu in the ores and Cr in fuchsite indicates the important role of mafic-ultramafic magmatism.

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