Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria.

Mycobacteria share with other actinomycetes the ability to produce large quantities of triacylglycerol (TAG), which accumulate as intracytoplasmic lipid inclusions (ILI) also known as lipid droplets (LD). Mycobacterium tuberculosis (M. tb), the etiologic agent of tuberculosis, acquires fatty acids from the human host which are utilized to synthesize TAG, subsequently stored in the form of ILI to meet the carbon and nutrient requirements of the bacterium during long periods of persistence. However, environmental factors governing mycobacterial ILI formation and degradation remain poorly understood. Herein, we demonstrated that in the absence of host cells, carbon excess and nitrogen starvation promote TAG accumulation in the form of ILI in M. smegmatis and M. abscessus, used as surrogate species of M. tb. Based on these findings, we developed a simple and reversible in vitro model to regulate ILI biosynthesis and hydrolysis in mycobacteria. We also showed that TAG formation is tgs1 dependent and that lipolytic enzymes mediate TAG breakdown. Moreover, we confirmed that the nitrogen-deprived and ILI-rich phenotype was associated with an increased tolerance towards several drugs used for treating mycobacterial infections. Importantly, we showed that the presence of ILI substantially enhanced the bacterial burden and granuloma abundance in zebrafish embryos infected with lipid-rich M. abscessus as compared to embryos infected with lipid-poor M. abscessus, suggesting that ILI are actively contributing to mycobacterial virulence and pathogenesis

A Candidate M31/M32 Intergalactic Microlensing Event

We report the discovery of a microlensing candidate projected 2'54" from the center of M32, on the side closest to M31. The blue color (R-I= 0.00 +/- 0.14) of the source argues strongly that it lies in the disk of M31, while the proximity of the line of sight to M32 implies that this galaxy is the most likely host of the lens. If this interpretation is correct, it would confirm previous arguments that M32 lies in front of M31. We estimate that of order one such event or less should be present in the POINT-AGAPE data base. If more events are discovered in this direction in a dedicated experiment, they could be used to measure the mass function of M32 up to an unknown scale factor. By combining microlensing observations of a binary-lens event with a measurement of the M31-M32 relative proper motion using the astrometric satellites SIM or GAIA, it will be possible to measure the physical separation of M31 and M32, the last of the six phase-space coordinates needed to assign M32 an orbit.Comment: Submitted to ApJ Letters. 13 pages, 2 figure

Antimicrobial use in European acute care hospitals : results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are lifesaving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016–17, we performed the second pointprevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2–31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials.peer-reviewe

Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4 <sup>+</sup> T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity

A database of the coseismic effects following the 30 October 2016 Norcia earthquake in Central Italy

We provide a database of the coseismic geological surface effects following the Mw 6.5 Norcia earthquake that hit central Italy on 30 October 2016. This was one of the strongest seismic events to occur in Europe in the past thirty years, causing complex surface ruptures over an area of >400 km 2. The database originated from the collaboration of several European teams (Open EMERGEO Working Group; about 130 researchers) coordinated by the Istituto Nazionale di Geofisica e Vulcanologia. The observations were collected by performing detailed field surveys in the epicentral region in order to describe the geometry and kinematics of surface faulting, and subsequently of landslides and other secondary coseismic effects. The resulting database consists of homogeneous georeferenced records identifying 7323 observation points, each of which contains 18 numeric and string fields of relevant information. This database will impact future earthquake studies focused on modelling of the seismic processes in active extensional settings, updating probabilistic estimates of slip distribution, and assessing the hazard of surface faulting

Beyond the public and private divide: Remapping transnational climate governance in de 21th century

This article provides a first step towards a better theoretical and empirical knowledge of the emerging arena of transnational climate governance. The need for such a re-conceptualization emerges from the increasing relevance of non-state and transnational approaches towards climate change mitigation at a time when the intergovernmental negotiation process has to overcome substantial stalemate and the international arena becomes increasingly fragmented. Based on a brief discussion of the increasing trend towards transnationalization and functional segmentation of the global climate governance arena, we argue that a remapping of climate governance is necessary and needs to take into account different spheres of authority beyond the public and international. Hence, we provide a brief analysis of how the public/private divide has been conceptualized in Political Science and International Relations. Subsequently, we analyse the emerging transnational climate governance arena. Analytically, we distinguish between different manifestations of transnational climate governance on a continuum ranging from delegated and shared public-private authority to fully non-state and private responses to the climate problem. We suggest that our remapping exercise presented in this article can be a useful starting point for future research on the role and relevance of transnational approaches to the global climate crisis

The Dynamic Landscape of Novel Psychoactive Substance (NPS) Use in Ireland: Results from an Expert Consultation

In Ireland, legislators encountered a new phenomenon in 2005 onwards with the advent of ‘legal highs’ sold in headshops. Use of ‘legal highs’ containing herbal and synthetic new psychoactive substances (NPS) was not confined to problematic drug users, and included social recreational users. Legislative controls were enacted in 2010, 2011 and 2015. The study aimed to investigate expert perspectives on the NPS situation with regard to changing and emergent trends in use, health and social consequences and service implications. This brief report presents descriptive findings from a national consultation using a structured guide with experts in 2016. Four themes emerged and centred on; ‘Definitions of NPS used within Professional Roles’; ‘Professional Experiences of NPS‘; ‘Types of NPS Users, Sourcing and Consequences of Use’; and ‘Service Response.’ Findings underscored the mental health and addiction related consequences of NPS use, with prevention, clinical and treatment services ill- equipped to deal with the particular characteristics of this form of drug abuse. Enhanced strategies, services and clinical responses are warranted to address the challenges encountered. © 2016 Springer Science+Business Media New Yor