A One Health Perspective on Salmonella enterica Serovar Infantis, an Emerging Human Multidrug-Resistant Pathogen

Salmonella enterica serovar Infantis presents an ever-increasing threat to public health because of its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). We analyzed whole-genome sequences of 5,284 Salmonella Infantis strains from 74 countries, isolated during 1989-2020 from a wide variety of human, animal, and food sources, to compare genetic phylogeny, AMR determinants, and plasmid presence. The global Salmonella Infantis population structure diverged into 3 clusters: a North American cluster, a European cluster, and a global cluster. The levels of AMR varied by Salmonella Infantis cluster and by isolation source; 73% of poultry isolates were multidrug resistant, compared with 35% of human isolates. This finding correlated with the presence of the pESI megaplasmid; 71% of poultry isolates contained pESI, compared with 32% of human isolates. This study provides key information for public health teams engaged in reducing the spread of this pathogen

Revealing the source of Jupiter’s x-ray auroral flares

Jupiter’s rapidly rotating, strong magnetic field provides a natural laboratory that is key to understanding the dynamics of high-energy plasmas. Spectacular auroral x-ray flares are diagnostic of the most energetic processes governing magnetospheres but seemingly unique to Jupiter. Since their discovery 40 years ago, the processes that produce Jupiter’s x-ray flares have remained unknown. Here, we report simultaneous in situ satellite and space-based telescope observations that reveal the processes that produce Jupiter’s x-ray flares, showing surprising similarities to terrestrial ion aurora. Planetary-scale electromagnetic waves are observed to modulate electromagnetic ion cyclotron waves, periodically causing heavy ions to precipitate and produce Jupiter’s x-ray pulses. Our findings show that ion aurorae share common mechanisms across planetary systems, despite temporal, spatial, and energetic scales varying by orders of magnitude

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences

Be Free? The European Union's post-Arab Spring Women's Empowerment as Neoliberal Governmentality

This article analyses post-Arab Spring EU initiatives to promote women's empowerment in the Southern Mediterranean region. Inspired by Foucauldian concepts of governmentality, it investigates empowerment as a technology of biopolitics that is central to the European neoliberal model of governance. In contrast to dominant images such as normative power Europe that present the EU as a norm-guided actor promoting political liberation, the article argues that the EU deploys a concept of functional freedom meant to facilitate its vision of economic development. As a consequence, the alleged empowerment of women based on the self-optimisation of individuals and the statistical control of the female population is a form of bio-power. In this regard, empowerment works as a governmental technology of power instead of offering a measure to foster fundamental structural change in Middle Eastern and North African (MENA) societies. The EU therefore fails in presenting and promoting an alternative normative political vision distinct from the incorporation of women into the hierarchy of the existing market society

Pathogen-Responsive Expression of a Putative ATP-Binding Cassette Transporter Gene Conferring Resistance to the Diterpenoid Sclareol Is Regulated by Multiple Defense Signaling Pathways in Arabidopsis

The ATP-binding cassette (ABC) transporters are encoded by large gene families in plants. Although these proteins are potentially involved in a number of diverse plant processes, currently, very little is known about their actual functions. In this paper, through a cDNA microarray screening of anonymous cDNA clones from a subtractive library, we identified an Arabidopsis gene (AtPDR12) putatively encoding a member of the pleiotropic drug resistance (PDR) subfamily of ABC transporters. AtPDR12 displayed distinct induction profiles after inoculation of plants with compatible and incompatible fungal pathogens and treatments with salicylic acid, ethylene, or methyl jasmonate. Analysis of AtPDR12 expression in a number of Arabidopsis defense signaling mutants further revealed that salicylic acid accumulation, NPR1 function, and sensitivity to jasmonates and ethylene were all required for pathogen-responsive expression of AtPDR12. Germination assays using seeds from an AtPDR12 insertion line in the presence of sclareol resulted in lower germination rates and much stronger inhibition of root elongation in the AtPDR12 insertion line than in wild-type plants. These results suggest that AtPDR12 may be functionally related to the previously identified ABC transporters SpTUR2 and NpABC1, which transport sclareol. Our data also point to a potential role for terpenoids in the Arabidopsis defensive armory

Genetic characterization of Salmonella Infantis from South Africa, 2004–2016

Salmonella Infantis is presenting an increasing risk to public health. Of particular concern are the reports of pESI, a multidrug resistance (MDR) encoding megaplasmid, in isolates from multiple countries, but little is known about its presence or diversity in South Africa. Whole genome sequences of 387 S. Infantis isolates from South Africa (2004–2020) were analysed for genetic phylogeny, recombination frequency, antimicrobial resistance (AMR) determinants, plasmid presence and overall gene content. The population structure of South African S. Infantis was substantially different to S. Infantis reported elsewhere; only two thirds of isolates belonged to eBG31, while the remainder were identified as eBG297, a much rarer group globally. Significantly higher levels of recombination were observed in the eBG297 isolates, which was associated with the presence of prophages. The majority of isolates were putatively susceptible to antimicrobials (335/387) and lacked any plasmids (311/387); the megaplasmid pESI was present in just one isolate. A larger proportion of eBG31 isolates, 19% (49/263), contained at least one AMR determinant, compared to eBG297 at 2% (3/124). Comparison of the pan-genomes of isolates from either eBG identified 943 genes significantly associated with eBG, with 43 found exclusively in eBG31 isolates and 34 in eBG297 isolates. This, along with the single nucleotide polymorphism distance and difference in resistance profiles, suggests that eBG31 and eBG297 isolates occupy different niches within South Africa. If antibiotic-resistant S. Infantis emerges in South Africa, probably through the spread of the pESI plasmid, treatment of this infection would be compromised

The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods

ChEMBL (https://www.ebi.ac.uk/chembl/) is a manually curated, high-quality, large-scale, open, FAIR and Global Core Biodata Resource of bioactive molecules with drug-like properties, previously described in the 2012, 2014, 2017 and 2019 Nucleic Acids Research Database Issues. Since its introduction in 2009, ChEMBL’s content has changed dramatically in size and diversity of data types. Through incorporation of multiple new datasets from depositors since the 2019 update, ChEMBL now contains slightly more bioactivity data from deposited data vs data extracted from literature. In collaboration with the EUbOPEN consortium, chemical probe data is now regularly deposited into ChEMBL. Release 27 made curated data available for compounds screened for potential anti-SARS-CoV-2 activity from several large-scale drug repurposing screens. In addition, new patent bioactivity data have been added to the latest ChEMBL releases, and various new features have been incorporated, including a Natural Product likeness score, updated flags for Natural Products, a new flag for Chemical Probes, and the initial annotation of the action type for ∼270 000 bioactivity measurements.ISSN:1362-4962ISSN:0301-561

Towards Unifying Jupiter’s X-rays with Radio, UV, Magnetic Field and Plasma Observations

In 1979, while the Voyager spacecraft were undertaking their paradigm-shifting multi-instrument explorations of the Jovian system, the Einstein X-ray observatory was also taking the first X-ray images of the planet (Metzger et al. 1983). Two decades later, the launch of the highly complementary Chandra and XMM-Newton X-ray observatories ushered in the modern era of X-ray astronomy. These cutting-edge astrophysics platforms uncovered a treasure trove of high energy astrophysical emissions from Jupiter. In particular, at the poles, they revealed a variety of vibrant aurorae: impulsive auroral flares which occur with a regular periodic beat every few 10s of minutes (Gladstone et al. 2002); flickering dim ion aurora (Dunn et al. 2020); electron bremsstrahlung aurora from along the main emission (Branduardi-Raymont et al. 2004; 2008) and hints of a transient electron aurora coincident with auroral injection events (Wibisono et al. 2021). In this talk, we explore connections between these X-ray auroral emissions and in-situ waves, plasma and magnetic field measurements by Juno (e.g. Yao & Dunn et al. 2021) and UV observations by the Hubble Space Telescope. We showthat the impulsive bursts of auroral X-rays share the same periodicity with kHz radio emissions and UV flares from the auroral zone and electromagnetic ion cyclotron waves, and anti-phase variations in the plasma and magnetic field, which may be indicative of slow mode or mirror mode waves. We will speculate on how these shared multi-waveband periodicities may be causally linked. We will also show overlaid X-ray and UV aurora videos, that explore further auroral connections between the UV and X-ray aurora, highlighting shared morphology and timing signatures between the two wavebands. Particularly, this reveals connections between emissions in the active region, on the boundary of the swirl region and in the dark polar region. Finally, we close the talk by touching on other potentially transformative X-ray capabilities for the outer planets including: direct imaging of the radiation belts by Suzaku (e.g. Numazawa et al. 2021), direct imaging of planetary magnetosheaths, and the elemental fingerprint fluorescence glow from the surfaces of the Galilean satellites, produced through moon-plasma interactions (e.g. Nulsen et al. 2020)

The Global Phosphorylation Landscape of SARS-CoV-2 Infection

International audienceThe causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies