NF-κB activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infection

Tolerance to bacterial components represents an essential regulatory mechanism during bacterial infection. Bacterial lipoprotein (BLP)-induced tolerance confers protection against microbial sepsis by attenuating inflammatory responses and augmenting antimicrobial activity in innate phagocytes. It has been well-documented that BLP tolerance-attenuated proinflammatory cytokine production is associated with suppressed TLR2 signalling pathway; however, the underlying mechanism(s) involved in BLP tolerance-enhanced antimicrobial activity is unclear. Here we report that BLP-tolerised macrophages exhibited accelerated phagosome maturation and enhanced bactericidal activity upon bacterial infection, with upregulated expression of membrane-trafficking regulators and lysosomal enzymes. Notably, bacterial challenge resulted in a strong activation of NF-κB pathway in BLP-tolerised macrophages. Importantly, activation of NF-κB pathway is critical for BLP tolerance-enhanced antimicrobial activity, as deactivation of NF-κB in BLP-tolerised macrophages impaired phagosome maturation and intracellular killing of the ingested bacteria. Finally, activation of NF-κB pathway in BLP-tolerised macrophages was dependent on NOD1 and NOD2 signalling, as knocking-down NOD1 and NOD2 substantially inhibited bacteria-induced activation of NF-κB and overexpression of Rab10 and Acp5, two membrane-trafficking regulators and lysosomal enzymes contributed to BLP tolerance-enhanced bactericidal activity. These results indicate that activation of NF-κB pathway is essential for BLP tolerance-augmented antimicrobial activity in innate phagocytes and depends primarily on both NOD1 and NOD2

Publisher Correction: Copper adparticle enabled selective electrosynthesis of n-propanol.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Boost Invariance and Multiplicity Dependence of the Charge Balance Functionin π+p\pi^{+}p and K+pK^{+}p Collisions at s=22\sqrt s= 22 GeV/c

Boost invariance and multiplicity dependence of the charge balance function are studied in \pi^{+}\rp and \rK^{+}\rp collisions at 250 GeV/$c$ incident beam momentum. Charge balance, as well as charge fluctuations, are found to be boost invariant over the whole rapidity region, but both depend on the size of the rapidity window. It is also found that the balance function becomes narrower with increasing multiplicity, consistent with the narrowing of the balance function when centrality and/or system size increase, as observed in current relativistic heavy ion experiments.Comment: 4 pages, 5 figures, Revte

Extreme fire weather is the major driver of severe bushfires in southeast Australia

In Australia, the proportion of forest area that burns in a typical fire season is less than for other vegetation types. However, the 2019–2020 austral spring-summer was an exception, with over four times the previous maximum area burnt in southeast Australian temperate forests. Temperate forest fires have extensive socio-economic, human health, greenhouse gas emissions, and biodiversity impacts due to high fire intensities. A robust model that identifies driving factors of forest fires and relates impact thresholds to fire activity at regional scales would help land managers and fire-fighting agencies prepare for potentially hazardous fire in Australia. Here, we developed a machine-learning diagnostic model to quantify nonlinear relationships between monthly burnt area and biophysical factors in southeast Australian forests for 2001–2020 on a 0.25° grid based on several biophysical parameters, notably fire weather and vegetation productivity. Our model explained over 80% of the variation in the burnt area. We identified that burnt area dynamics in southeast Australian forest were primarily controlled by extreme fire weather, which mainly linked to fluctuations in the Southern Annular Mode (SAM) and Indian Ocean Dipole (IOD), with a relatively smaller contribution from the central Pacific El Nino Southern Oscillation (ENSO). Our fire diagnostic model and the non-linear relationships between burnt area and environmental covariates can provide useful guidance to decision-makers who manage preparations for an upcoming fire season, and model developers working on improved early warning systems for forest fires

Charge Fluctuations in \pi^{+}\rp and \rK^{+}\rp Collisions at 250 GeV/cc

We report on measurements of event-by-event charge fluctuations in \pi^{+}\rp and \rK^{+}\rp collisions at 250 GeV/$c$. The dependence of these fluctuations on the size of the rapidity windows are presented for the first time in the full phase space domain. The corrections for the influence of global charge conservation and leading-particle stopping are tested by the data. The discrepancy due to incomplete correction given by STAR and PHENIX are estimated. The dependence of the fluctuations on the position of the rapidity bin and on the multiplicity at different rapidity windows are also presented.Comment: 4pages, 3figure

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.

Crystal Structure of EHEC Intimin: Insights into the Complementarity between EPEC and EHEC

Enterohaemorrhagic E. coli (EHEC) O157:H7 is a primary food-borne bacterial pathogen capable of causing life-threatening human infections which poses a serious challenge to public health worldwide. Intimin, the bacterial outer-membrane protein, plays a key role in the initiating process of EHEC infection. This activity is dependent upon translocation of the intimin receptor (Tir), the intimin binding partner of the bacteria-encoded host cell surface protein. Intimin has attracted considerable attention due to its potential function as an antibacterial drug target. Here, we report the crystal structure of the Tir-binding domain of intimin (Int188) from E. coli O157:H7 at 2.8 Å resolution, together with a mutant (IntN916Y) at 2.6 Å. We also built the structural model of EHEC intimin-Tir complex and analyzed the key binding residues. It suggested that the binding pattern of intimin and Tir between EHEC and Enteropathogenic E. coli (EPEC) adopt a similar mode and they can complement with each other. Detailed structural comparison indicates that there are four major points of structural variations between EHEC and EPEC intimins: one in Domain I (Ig-like domain), the other three located in Domain II (C-type lectin-like domain). These variations result in different binding affinities. These findings provide structural insight into the binding pattern of intimin to Tir and the molecular mechanism of EHEC O157: H7

Crystal Structure of EHEC Intimin: Insights into the Complementarity between EPEC and EHEC

Enterohaemorrhagic E. coli (EHEC) O157:H7 is a primary food-borne bacterial pathogen capable of causing life-threatening human infections which poses a serious challenge to public health worldwide. Intimin, the bacterial outer-membrane protein, plays a key role in the initiating process of EHEC infection. This activity is dependent upon translocation of the intimin receptor (Tir), the intimin binding partner of the bacteria-encoded host cell surface protein. Intimin has attracted considerable attention due to its potential function as an antibacterial drug target. Here, we report the crystal structure of the Tir-binding domain of intimin (Int188) from E. coli O157:H7 at 2.8 Å resolution, together with a mutant (IntN916Y) at 2.6 Å. We also built the structural model of EHEC intimin-Tir complex and analyzed the key binding residues. It suggested that the binding pattern of intimin and Tir between EHEC and Enteropathogenic E. coli (EPEC) adopt a similar mode and they can complement with each other. Detailed structural comparison indicates that there are four major points of structural variations between EHEC and EPEC intimins: one in Domain I (Ig-like domain), the other three located in Domain II (C-type lectin-like domain). These variations result in different binding affinities. These findings provide structural insight into the binding pattern of intimin to Tir and the molecular mechanism of EHEC O157: H7

A Holistic Perspective on the Dynamics of G035.39-00.33 : The Interplay between Gas and Magnetic Fields

Magnetic field plays a crucial role in shaping molecular clouds and regulating star formation, yet the complete information on the magnetic field is not well constrained owing to the limitations in observations. We study the magnetic field in the massive infrared dark cloud G035.39-00.33 from dust continuum polarization observations at 850 mu m with SCUBA-2/POL-2 at JCMT for the first time. The magnetic field tends to be perpendicular to the densest part of the main filament (F-M), whereas it has a less defined relative orientation in the rest of the structure, where it tends to be parallel to some diffuse regions. A mean plane-of-the-sky magnetic field strength of similar to 50 mu G for F-M is obtained using the Davis-Chandrasekhar-Fermi method. Based on (CO)-C-13 (1-0) line observations, we suggest a formation scenario of F-M due to large-scale (similar to 10 pc) cloud-cloud collision. Using additional NH3 line data, we estimate that F-M will be gravitationally unstable if it is only supported by thermal pressure and turbulence. The northern part of F-M, however, can be stabilized by a modest additional support from the local magnetic field. The middle and southern parts of F-M are likely unstable even if the magnetic field support is taken into account. We claim that the clumps in F-M may be supported by turbulence and magnetic fields against gravitational collapse. Finally, we identified for the first time a massive (similar to 200 M-circle dot, collapsing starless clump candidate, "c8," in G035.39-00.33. The magnetic field surrounding "c8" is likely pinched, hinting at an accretion flow along the filament.Peer reviewe