Decomposing virulence to understand bacterial clearance in persistent infections

Following an infection, hosts cannot always clear the pathogen, instead either dying or surviving with a persistent infection. Such variation is ecologically and evolutionarily important because it can affect infection prevalence and transmission, and virulence evolution. However, the factors causing variation in infection outcomes, and the relationship between clearance and virulence are not well understood. Here we show that sustained persistent infection and clearance are both possible outcomes across bacterial species showing a range of virulence in Drosophila melanogaster. Variation in virulence arises because of differences in the two components of virulence: bacterial infection intensity inside the host (exploitation), and the amount of damage caused per bacterium (per parasite pathogenicity). As early-phase exploitation increased, clearance rates later in the infection decreased, whereas there was no apparent effect of per parasite pathogenicity on clearance rates. Variation in infection outcomes is thereby determined by how virulence – and its components – relate to the rate of pathogen clearance. Taken together we demonstrate that the virulence decomposition framework is broadly applicable and can provide valuable insights into host-pathogen interactions

Managing Collaborative Development of Artificial Intelligence: Lessons from the Field

Artificial intelligence (AI) promises businesses superior decisions that outperform those of domain experts. However, AI systems may fail on the ground when they are not developed in collaboration with the experts they seek to bypass. This raises the question of how to manage the collaborative development of AI. Building on a comparative field study, we reveal three key challenges of collaborative AI development in the area of consulting, hiring, and radiology. Based on these findings, we derive guidelines for managers that help them to facilitate the close engagement between AI developers and experts

Contrasted histories of organelle and nuclear genomes underlying physiological diversification in a grass species: Intraspecific dispersal of C4 physiology

C 4 photosynthesis evolved multiple times independently in angiosperms, but most origins are relatively old so that the early events linked to photosynthetic diversification are blurred. The grass Alloteropsis semialata is an exception, as this species encompasses C 4 and non-C 4 populations. Using phylogenomics and population genomics, we infer the history of dispersal and secondary gene flow before, during and after photosynthetic divergence in A. semialata. We further analyse the genome composition of individuals with varied ploidy levels to establish the origins of polyploids in this species. Detailed organelle phylogenies indicate limited seed dispersal within the mountainous region of origin and the emergence of a C 4 lineage after dispersal to warmer areas of lower elevation. Nuclear genome analyses highlight repeated secondary gene flow. In particular, the nuclear genome associated with the C 4 phenotype was swept into a distantly related maternal lineage probably via unidirectional pollen flow. Multiple intraspecific allopolyploidy events mediated additional secondary genetic exchanges between photosynthetic types. Overall, our results show that limited dispersal and isolation allowed lineage divergence, with photosynthetic innovation happening after migration to new environments, and pollen-mediated gene flow led to the rapid spread of the derived C 4 physiology away from its region of origin.This study was funded by the European Research Council (grant no. ERC-2014-STG-638333), the Royal Society (grant no. RGF\EA\181050) and has benefited from ‘Investissements d'Avenir' grants managed by the Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-25-01 and TULIP, ref. ANR-10-LABX-41). Edinburgh Genomics, which contributed to the sequencing, is partly supported through core grants from the NERC (grant no. R8/H10/ 56), MRC (grant no. MR/K001744/1) and BBSRC (grant no. BB/ J004243/1). P.A.C. is funded by a Royal Society University Research Fellowship (grant no. URF\R\180022).Abstract 1. Introduction 2. Materials and methods (a) Sampling, sequencing and data filtering (b) Genome sizing and carbon isotope analyses (c) Assembly of organelle genomes and molecular dating (d) Phylogenetic analyses of the nuclear genome (e) Genetic structure (f) Genome composition 3. Results (a) Genome sizes (b) Time-calibrated organelle phylogenies (c) Nuclear phylogeny (d) Population structure and genome composition 4. Discussion (a) Limited seed dispersal in the region of origin (b) Widespread pollen flow and sweep of the C4 nuclear genome (c) Recurrent hybridization and polyploidization 5. Concluding remarks Data accessibility Authors' contributions Competing interests Funding Acknowledgements Footnote

The Associated Decision and Management Factors on Cattle Tick Level of Infestation in Two Tropical Areas of Ecuador.

peer reviewedDecision-making on tick control practices is linked to the level of knowledge about livestock farming and to the social context in which individuals practice them. Tick infestation is one of the main problems in tropical livestock production. The objective of this study was to characterize tick-control related practices in two tropical livestock areas and their potential association with the level of tick infestation. A total of 139 farms were included in this survey. To determine this association, a multivariate logistic regression model was used. A stepwise model selection procedure was used and model validation was tested. Cattle husbandry as a main activity, the use of external paddocks, the use of amitraz, and the lack of mechanization on the farm were related with high tick infestation. On the other hand, owner involvement in the preparation of acaricide solution was identified as a protective factor against high tick infestation. At animal level, age (old), body condition status (thin), and lactation were also associated with high tick infestations, while Bos primigenius indicus cattle and their crosses reduced the probability of high tick infestations. The factors studied, such as herd size, education level of the owners, and veterinary guidance, varied from farm to farm. Nonetheless, these differences did not generate changes in the level of tick infestation. According to the area under the receiver operating characteristic curve (AUC-ROC), the model at farm level predicts a high level of infestation, with an accuracy of 72.00% and high sensitivity. In addition, at animal level, crossbreeding with indicus cattle and breeding selection for host resistance will be useful against high tick infestation. Likewise, the implementation of programs of capacitation and research on tick control for farmers, cowboys, and vets in these areas is necessary

A Concerted Action of Engrailed and Gooseberry-Neuro in Neuroblast 6-4 Is Triggering the Formation of Embryonic Posterior Commissure Bundles

One challenging question in neurogenesis concerns the identification of cues that trigger axonal growth and pathfinding to form stereotypic neuronal networks during the construction of a nervous system. Here, we show that in Drosophila, Engrailed (EN) and Gooseberry-Neuro (GsbN) act together as cofactors to build the posterior commissures (PCs), which shapes the ventral nerve cord. Indeed, we show that these two proteins are acting together in axon growth and midline crossing, and that this concerted action occurs at early development, in neuroblasts. More precisely, we identified that their expressions in NB 6-4 are necessary and sufficient to trigger the formation of the PCs, demonstrating that segmentation genes such as EN and GsbN play a crucial role in the determination of NB 6-4 in a way that will later influence growth and guidance of all the axons that form the PCs. We also demonstrate a more specific function of GsbN in differentiated neurons, leading to fasciculations between axons, which might be required to obtain PC mature axon bundles

Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease

Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils "plucked" intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events

Grado de infestación de garrapatas asociado con factores individuales del ganado bovino en ganaderías subtropicales del Ecuador

En Ecuador, Rhipicephalus microplus es la principal garrapata que afecta al ganado bovino, cuyo control exige conocer su comportamiento. El objetivo de este estudio fue evaluar el grado de infestación de R. microplus, examinando la ubicación anatómica de las garrapatas y su posible asociación con factores intrínsecos de los animales como son el estado general de salud, condición corporal, color del pelaje. Se llevaron a cabo cuatro muestreos cada tres meses en un total de 15 fincas en el Noroccidente de Pichincha (localidad1) y 15 fincas en el Valle de los Quijos (localidad2). Las garrapatas mayores a 0.5cm fueron contadas en 5 animales escogidos al azar. Como resultados, en cuatro muestreos realizados en las dos localidades, se encontró un promedio de 99.39 ± SD156.28(0–1426) garrapatas por animal, y un promedio de 108.8±SD179.43(0–1426) y 88.2 ± SD122.80(0–824) para la localidad 1 y 2, respectivamente. Solo la variable "salud aparente de piel y pelaje" mostró una asociación estadística positiva, con un valor P<0.05 y odds ratios de 5.13(IC 95%: 2.04-13.65) y 25.83(IC 95%: 7.63-109.39) en las categorías "regular" y "malo" respecto del estado considerado como bueno. Además, la categoría animal denominado "viejo" en la variable Edad tuvo un valor P=0.05 y un odds ratio de 2.88(IC 95%: 1.04-8.80). Anatómicamente se encontraron más garrapatas en la zona anatómica correspondiente a muslos, ubre posterior, pierna y corvejón, con un promedio de 38.52±SD70.17(0–448) garrapatas. En conclusión, la infestación con garrapatas representa un problema grave que afecta a las ganaderías de regiones tropicales del país, este estudio ayuda a direccionar de mejor manera las formas y prácticas de control sobre los bovinos

An economic evaluation of cattle tick acaricide-resistances and the financial losses in subtropical dairy farms of Ecuador: A farm system approach.

peer reviewedEstimates of economic losses in cattle due to tick infestations in subtropical areas are limited, such as in Ecuador. Ticks affect animal production and health, but those direct effects are difficult to estimate since financial exercises carried out in farms consider both costs of the inputs and revenues. This study aims to quantify the costs of inputs involved in milk production and to know the role of acaricide treatment in the production costs on dairy farms in subtropical zones using a farming system approach. Regression and classification trees were used to study the relationship between tick control, acaricide resistance and the presence of high level of tick infestation in the farm system. Even though there was no significant direct association between high levels of tick infestation and the presence of acaricide resistance in ticks, a more complex structure for resistances operates in the manifestation of high tick infestation involving levels of farm technology and no acaricide resistance. Farms with higher levels of technology allocate a lower percentage of sanitary expenses to control ticks (13.41%) in comparison to semi-technified (23.97%) and non-technified farms (32.49%). Likewise, more technified and bigger herds have a lower annual expenditure on acaricide treatment (1.30% of the production budget equivalent to 8.46 USD per animal) compared to non-technified farms where it can represent more than 2.74% of the production budget and where the absence of cypermethrin resistance increases the treatment cost to 19.50 USS per animal annually. These results can motivate the development of information campaigns and control programmes targeted to the reality of small and medium farms that are the most affected in terms of the money they invest in controlling ticks

The epidemiology of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in community-living seniors: protocol of the MemoVie cohort study, Luxembourg

BACKGROUND: Cognitive impairment and Alzheimer’s disease (AD) are increasingly considered a major public health problem. The MemoVie cohort study aims to investigate the living conditions or risk factors under which the normal cognitive capacities of the senior population in Luxembourg (≥ 65 year-old) evolve (1) to mild cognitive impairment (MCI) – transitory non-clinical stage – and (2) to AD. Identifying MCI and AD predictors undeniably constitutes a challenge in public health in that it would allow interventions which could protect or delay the occurrence of cognitive disorders in elderly people. In addition, the MemoVie study sets out to generate hitherto unavailable data, and a comprehensive view of the elderly population in the country. METHODS/DESIGN: The study has been designed with a view to highlighting the prevalence in Luxembourg of MCI and AD in the first step of the survey, conducted among participants selected from a random sample of the general population. A prospective cohort is consequently set up in the second step, and appropriate follow-up of the non-demented participants allows improving the knowledge of the preclinical stage of MCI. Case-control designs are used for cross-sectional or retrospective comparisons between outcomes and biological or clinical factors. To ensure maximal reliability of the information collected, we decided to opt for structured face to face interviews. Besides health status, medical and family history, demographic and socio-cultural information are explored, as well as education, habitat network, social behavior, leisure and physical activities. As multilingualism is expected to challenge the cognitive alterations associated with pathological ageing, it is additionally investigated. Data relative to motor function, including balance, walk, limits of stability, history of falls and accidents are further detailed. Finally, biological examinations, including ApoE genetic polymorphism are carried out. In addition to standard blood parameters, the lipid status of the participants is subsequently determined from the fatty acid profiles in their red blood cells. The study obtained the legal and ethical authorizations. DISCUSSION: By means of the multidisciplinary MemoVie study, new insights into the onset of cognitive impairment during aging should be put forward, much to the benefit of intervention strategies as a whole