Dioxygen controls the nitrosylation reactions of a protein-bound [4Fe4S] cluster

Iron–sulfur clusters are exceptionally tuneable protein cofactors, and as one of their many roles they are involved in biological responses to nitrosative stress. Both iron–sulfur proteins and synthetic model clusters are extremely sensitive to nitrosylation, tending towards rapid multi-step reaction and cluster degradation. Reaction of protein-bound iron–sulfur clusters with nitric oxide can be stopped at partial nitrosylation in vivo, and repair of protein-bound nitrosylated clusters is possible in the cellular environment. We have used a combination of infrared, EPR, and UV-visible spectroscopies to show that a model [4Fe4S] cluster-containing protein, A. ferroxidans high potential iron–sulfur protein (HiPIP), reacts with NO to give a product mixture dominated by Roussin's Black Salt (RBS) and Roussin's Red Ester (RRE) species. We have shown that O2 plays a critical role in controlling the major product of nitrosylation, with RBS-like products favoured under strictly anaerobic conditions and RRE favoured in the presence of trace O2. Moreover, addition of trace O2 to anaerobically nitrosylated samples induces conversion of RBS-like products to RRE. These findings may have implications for mechanisms of iron–sulfur cluster repair following nitrosative stress, suggest a crucial role for trace O2, and provide an important link between nitrosylation chemistry of iron–sulfur proteins and the well-established reactivity of synthetic iron–sulfur clusters

Flavoured jets with exact anti-ktk_t kinematics and tests of infrared and collinear safety

We propose extensions of the anti-$k_t$ and Cambridge/Aachen hierarchical jet clustering algorithms that are designed to retain the exact jet kinematics of these algorithms, while providing an infrared-and-collinear-safe definition of jet flavour at any fixed order in perturbation theory. Central to our approach is a new technique called Interleaved Flavour Neutralisation (IFN), whereby the treatment of flavour is integrated with, but distinct from, the kinematic clustering. IFN allows flavour information to be meaningfully accessed at each stage of the clustering sequence, which enables a consistent assignment of flavour both to individual jets and to their substructure. We validate the IFN approach using a dedicated framework for fixed-order tests of infrared and collinear safety, which also reveals unanticipated issues in earlier approaches to flavoured jet clustering. We briefly explore the phenomenological impact of IFN with anti-$k_t$ jets for benchmark tasks at the Large Hadron Collider.Comment: 36 pages, 27 figures, 1 table, code available from https://github.com/jetflav/IFNPlugi

The S phase checkpoint promotes the Smc5/6 complex dependent SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε

Replication fork stalling and accumulation of single-stranded DNA trigger the S phase checkpoint, a signalling cascade that, in budding yeast, leads to the activation of the Rad53 kinase. Rad53 is essential in maintaining cell viability, but its targets of regulation are still partially unknown. Here we show that Rad53 drives the hyper-SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε, principally following replication forks stalling induced by nucleotide depletion. Pol2 is the main target of SUMOylation within the replisome and its modification requires the SUMO-ligase Mms21, a subunit of the Smc5/6 complex. Moreover, the Smc5/6 complex co-purifies with Pol ε, independently of other replisome components. Finally, we map Pol2 SUMOylation to a single site within the N-terminal catalytic domain and identify a SUMO-interacting motif at the C-terminus of Pol2. These data suggest that the S phase checkpoint regulate Pol ε during replication stress through Pol2 SUMOylation and SUMO-binding abilit

DNA metabarcoding analysis of three material types to reveal Joro spider (Trichonephila clavata) trophic interactions and web capture

Funding for MQ was provided by FICYT and “Plan de Ciencia, Tecnologia e Innovacion 2018–2022” from the Government of Asturias (Grant AYUD/2021/58607)

A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles

Eukaryotic cells use a multi-layered immune response to combat intracellular pathogens. The ubiquitin ligase ZNFX1 has emerged as a crucial yet little understood player that regulates the immune response while protecting against RNA viruses. Our study unveils the molecular mechanism of ZNFX1, mediated by the joint activity of a helicase serving as a nucleic acid sensor and a non-conventional E3 module featuring a split active site. We demonstrate that single-stranded RNA stimulates E3 activity by fostering dimerization of ZNFX1 subunits that translocate along nucleic acid tracks. Juxtaposed E3 domains complement each other, leading to the ubiquitination of ZNFX1 itself and engaged RNA molecules, while clustering nucleic acids into dense nucleoprotein particles. We show that the E3 ligase activity of ZNFX1 protects cells during an immune response and propose that ubiquitin-coated particles formed by ZNFX1 represent part of an ancient mechanism to regulate both foreign and host RNA in the cell

Flavoured jet algorithms: a comparative study

The accurate identification of heavy-flavour jets — those which originate from bottom or charm quarks — is crucial for precision studies of the Standard Model and searches for new physics. However, assigning flavour to jets presents significant challenges, primarily due to issues with infrared and collinear (IRC) safety. This paper aims to address these challenges by evaluating recently-proposed jet algorithms designed to be IRC-safe and applicable in high-precision measurements. We compare these algorithms across benchmark heavy-flavour production processes and kinematic regimes that are relevant for LHC phenomenology. Exploiting both fixed-order calculations in QCD as well as parton shower simulations, we analyse the infrared sensitivity of these new algorithms at different stages of the event evolution and compare to flavour labelling strategies currently adopted by LHC collaborations. The results highlight that, while all algorithms lead to more robust flavour assignments compared to current techniques, they vary in performance depending on the observable and energy regime. The study lays groundwork for robust, flavour-aware jet analyses in current and future collider experiments to maximise the physics potential of experimental data by reducing discrepancies between theoretical and experimental methods

The game itself?:Towards a Hermeneutics of Computer Games

In this paper, we reassess the notion and current state of ludohermeneutics in game studies, and propose a more solid foundation for how to conduct hermeneutic game analysis. We argue that there can be no ludo-hermeneutics as such, and that every game interpretation rests in a particular game ontology, whether implicit or explicit. The quality of this ontology, then, determines a vital aspect of the quality of the analysis

Increased Expression of Bcl11b Leads to Chemoresistance Accompanied by G1 Accumulation

BACKGROUND: The expression of BCL11B was reported in T-cells, neurons and keratinocytes. Aberrations of BCL11B locus leading to abnormal gene transcription were identified in human hematological disorders and corresponding animal models. Recently, the elevated levels of Bcl11b protein have been described in a subset of squameous cell carcinoma cases. Despite the rapidly accumulating knowledge concerning Bcl11b biology, the contribution of this protein to normal or transformed cell homeostasis remains open. METHODOLOGY/PRINCIPAL FINDINGS: Here, by employing an overexpression strategy we revealed formerly unidentified features of Bcl11b. Two different T-cell lines were forced to express BCL11B at levels similar to those observed in primary T-cell leukemias. This resulted in markedly increased resistance to radiomimetic drugs while no influence on death-receptor apoptotic pathway was observed. Apoptosis resistance triggered by BCL11B overexpression was accompanied by a cell cycle delay caused by accumulation of cells at G1. This cell cycle restriction was associated with upregulation of CDKN1C (p57) and CDKN2C (p18) cyclin dependent kinase inhibitors. Moreover, p27 and p130 proteins accumulated and the SKP2 gene encoding a protein of the ubiquitin-binding complex responsible for their degradation was repressed. Furthermore, the expression of the MYCN oncogene was silenced which resulted in significant depletion of the protein in cells expressing high BCL11B levels. Both cell cycle restriction and resistance to DNA-damage-induced apoptosis coincided and required the histone deacetylase binding N-terminal domain of Bcl11b. The sensitivity to genotoxic stress could be restored by the histone deacetylase inhibitor trichostatine A. CONCLUSIONS: The data presented here suggest a potential role of BCL11B in tumor survival and encourage developing Bcl11b-inhibitory approaches as a potential tool to specifically target chemoresistant tumor cells

Measurements of the production cross-sections of a Higgs boson in association with a vector boson and decaying into WW * with the ATLAS detector at s = 13 TeV

Measurements of the total and differential Higgs boson production cross-sections, via WH and ZH associated production using H → WW* → ℓνℓν and H → WW* → ℓνjj decays, are presented. The analysis uses proton-proton events delivered by the Large Hadron Collider at a centre-of-mass energy of 13 TeV and recorded by the ATLAS detector between 2015 and 2018. The data correspond to an integrated luminosity of 140 fb−1. The sum of the WH and ZH cross-sections times the H → WW* branching fraction is measured to be 0.44−0.09+0.10stat.−0.05+0.06syst. pb, in agreement with the Standard Model prediction. Higgs boson production is further characterised through measurements of the differential cross-section as a function of the transverse momentum of the vector boson and in the framework of Simplified Template Cross-Sections

Search for supersymmetry using vector boson fusion signatures and missing transverse momentum in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents a search for supersymmetric particles in models with highly compressed mass spectra, in events consistent with being produced through vector boson fusion. The search uses 140 fb−1 of proton-proton collision data at s = 13 TeV collected by the ATLAS experiment at the Large Hadron Collider. Events containing at least two jets with a large gap in pseudorapidity, large missing transverse momentum, and no reconstructed leptons are selected. A boosted decision tree is used to separate events consistent with the production of supersymmetric particles from those due to Standard Model backgrounds. The data are found to be consistent with Standard Model predictions. The results are interpreted using simplified models of R-parity-conserving supersymmetry in which the lightest supersymmetric partner is a bino-like neutralino with a mass similar to that of the lightest chargino and second-to-lightest neutralino, both of which are wino-like. Lower limits at 95% confidence level on the masses of next-to-lightest supersymmetric partners in this simplified model are established between 117 and 120 GeV when the lightest supersymmetric partners are within 1 GeV in mass