The genetic architecture of defence as resistance to and tolerance of bacterial infection in Drosophila melanogaster

Defence against pathogenic infection can take two forms: resistance and tolerance. Resistance is the ability of the host to limit a pathogen burden, whereas tolerance is the ability to limit the negative consequences of infection at a given level of infection intensity. Evolutionarily, a tolerance strategy that is independent of resistance could allow the host to avoid mounting a costly immune response and, theoretically, to avoid a co‐evolutionary arms race between pathogen virulence and host resistance. Biomedically, understanding the mechanisms of tolerance and how they relate to resistance could potentially yield treatment strategies that focus on health improvement instead of pathogen elimination. To understand the impact of tolerance on host defence and identify genetic variants that determine host tolerance, we defined genetic variation in tolerance as the residual deviation from a binomial regression of fitness under infection against infection intensity. We then performed a genomewide association study to map the genetic basis of variation in resistance to and tolerance of infection by the bacterium Providencia rettgeri. We found a positive genetic correlation between resistance and tolerance, and we demonstrated that the level of resistance is highly predictive of tolerance. We identified 30 loci that predict tolerance, many of which are in genes involved in the regulation of immunity and metabolism. We used RNAi to confirm that a subset of mapped genes have a role in defence, including putative wound repair genes grainy head and debris buster. Our results indicate that tolerance is not an independent strategy from resistance, but that defence arises from a collection of physiological processes intertwined with canonical immunity and resistance

Enhancing the significance of gravitational wave bursts through signal classification

The quest to observe gravitational waves challenges our ability to discriminate signals from detector noise. This issue is especially relevant for transient gravitational waves searches with a robust eyes wide open approach, the so called all- sky burst searches. Here we show how signal classification methods inspired by broad astrophysical characteristics can be implemented in all-sky burst searches preserving their generality. In our case study, we apply a multivariate analyses based on artificial neural networks to classify waves emitted in compact binary coalescences. We enhance by orders of magnitude the significance of signals belonging to this broad astrophysical class against the noise background. Alternatively, at a given level of mis-classification of noise events, we can detect about 1/4 more of the total signal population. We also show that a more general strategy of signal classification can actually be performed, by testing the ability of artificial neural networks in discriminating different signal classes. The possible impact on future observations by the LIGO-Virgo network of detectors is discussed by analysing recoloured noise from previous LIGO-Virgo data with coherent WaveBurst, one of the flagship pipelines dedicated to all-sky searches for transient gravitational waves

Presence of New Delhi metallo-β-lactamase gene (NDM-1) in a clinical isolate of Acinetobacter junii in Argentina

Here we report the presence of a clinically significant A. junii blaNDM-1 positive in a 38-year-old woman who was admitted to the emergency department with a fever and leg ulcers with signs of infection. The NDM-1 carbapenemase has been dramatically spread among Gram-negative bacilli, thus imposing a new challenge on the health system to fight bacterial infections.These data expand the number of Acinetobacter species harbouring blaNDM-1. The wide existence of Acinetobacter harbouring and dispersing this carbapenemase emphasizes the importance of non-previously recognized pathogens as reservoirs of dangerous resistance determinants. These resistance determinants can be later easily transferred to other menacing pathogens.Fil: Montaña, Sabrina Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cittadini, Roxana. Sanatorio Mater Dei; ArgentinaFil: Del Castillo M,. Sanatorio Mater Dei; ArgentinaFil: Uong, S.. California State University; Estados UnidosFil: Lazzaro, T.. California State University; Estados UnidosFil: Almuzara, Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Barberis, Claudia. Sanatorio Mater Dei; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Vay, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Ramírez, M. S.. California State University; Estados Unido

Mitigation of 42^{42}Ar/42^{42}K background for the GERDA Phase II experiment

Background coming from the $^{42}$Ar decay chain is considered to be one of the most relevant for the GERDA experiment, which aims to search of the neutrinoless double beta decay of $^{76}$Ge. The sensitivity strongly relies on the absence of background around the Q-value of the decay. Background coming from $^{42}$K, a progeny of $^{42}$Ar, can contribute to that background via electrons from the continuous spectrum with an endpoint of 3.5 MeV. Research and development on the suppression methods targeting this source of background were performed at the low-background test facility LArGe. It was demonstrated that by reducing $^{42}$K ion collection on the surfaces of the broad energy germanium detectors in combination with pulse shape discrimination techniques and an argon scintillation veto, it is possible to suppress the $^{42}$K background by three orders of magnitude. This is sufficient for Phase II of the GERDA experiment

Water-energy-ecosystem nexus in small run-of-river hydropower : Optimal design and policy

Acknowledgment This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Support from the Helmholtz Centre for Environmental Research - UFZ is gratefully acknowledged.Peer reviewedPublisher PD

Abobotulinumtoxina and rehabilitation vs rehabilitation alone in post-stroke spasticity: A cost-utility analysis

Objective: To investigate costs and quality-adjusted life years of rehabilitation combined with abobotulinumtoxinA (aboBoNT-A) (rehab/aboBoNT-A) vs rehabilitation alone (rehab) in post-stroke spasticity in Italy. Design: Based on both Italian National Health Service and societal perspectives, a 2-year cost-utility analysis model was performed. Subject/patients: The cost-utility analysis model considered hypothetical patients. Methods: The cost-utility analysis model was populated with data concerning demographics, disease severity, healthcare and non-healthcare resource consumption. Data were collected via a questionnaire administered to 3 highly experienced Italian physiatrists (864 out of 930 post-stroke spasticity patients on rehab/aboBoNT-A in total). Costs are expressed in Euro (\u20ac) based on the year 2018. Results: The cost to society (rounded to the nearest whole \u20ac) was \u20ac22,959 (rehab/aboBoNT-A) vs \u20ac11,866 (rehab). Italian National Health Servicefunded cost was \u20ac7,593 (rehab/aboBoNT-A) vs \u20ac1,793 (rehab). Over a period of 2 years rehab/aboBoNT-A outperforms rehab in terms of qualityadjusted life years gained (1.620 vs 1.150). The incremental cost-utility ratio was \u20ac12,341 (Italian National Health Service viewpoint) and \u20ac23,601 (societal viewpoint). Sensitivity analyses confirmed the robustness of the baseline results. Conclusion: Despite some limitations, the higher number of quality-adjusted life years gained vs rehab and the high probability of reaching a cost-utility ratio lower than the Italian informal acceptability range (\u20ac25,000-40,000) make rehab/aboBoNT-A a cost-effective healthcare programme for treating patients with post-stroke spasticity in Italy