Evolutionary Pathways and Trajectories in Antibiotic Resistance.

Evolution is the hallmark of life. Descriptions of the evolution of microorganisms have provided a wealth of information, but knowledge regarding "what happened" has precluded a deeper understanding of "how" evolution has proceeded, as in the case of antimicrobial resistance. The difficulty in answering the "how" question lies in the multihierarchical dimensions of evolutionary processes, nested in complex networks, encompassing all units of selection, from genes to communities and ecosystems. At the simplest ontological level (as resistance genes), evolution proceeds by random (mutation and drift) and directional (natural selection) processes; however, sequential pathways of adaptive variation can occasionally be observed, and under fixed circumstances (particular fitness landscapes), evolution is predictable. At the highest level (such as that of plasmids, clones, species, microbiotas), the systems' degrees of freedom increase dramatically, related to the variable dispersal, fragmentation, relatedness, or coalescence of bacterial populations, depending on heterogeneous and changing niches and selective gradients in complex environments. Evolutionary trajectories of antibiotic resistance find their way in these changing landscapes subjected to random variations, becoming highly entropic and therefore unpredictable. However, experimental, phylogenetic, and ecogenetic analyses reveal preferential frequented paths (highways) where antibiotic resistance flows and propagates, allowing some understanding of evolutionary dynamics, modeling and designing interventions. Studies on antibiotic resistance have an applied aspect in improving individual health, One Health, and Global Health, as well as an academic value for understanding evolution. Most importantly, they have a heuristic significance as a model to reduce the negative influence of anthropogenic effects on the environment.

Increasing the damping of oscillatory systems with an arbitrary number of time varying frequencies using fractional-order collocated feedback.

This paper studies the active damping of the oscillations of lightly damped linear systems whose parameters are indeterminate or may change through time. Systems with an arbitrary number of vibration modes are considered. Systems described by partial differential equations, that yield an infinite number of vibration modes, can also be included. In the case of collocated feedback, i.e. the sensor is placed at the same location of the actuator, a simple fractional order differentiation or integration of the measured signal is proposed that provides an effective control: (1) it guarantees a minimum phase margin or damping of the closed-loop system at all vibration modes, (2) this feature is robustly achieved, i.e., it is attained for very large variations or uncertainties of the oscillation frequencies of the system and (3) it is robust to spillover effects, i.e., to the unstabilizing effects of the vibration modes neglected in the controller design (especially important in infinite dimensional systems). Moreover, the sensitivity of the gain crossover frequency to such variations is assessed. Finally, these results are applied to the position control of a single link flexible robot. Simulated results are provided.

Plant growth-promoting traits of yeasts isolated from Spanish vineyards: benefits for seedling development.

It is known that some microorganisms can enhance plant development. However, the use of yeasts as growth-promoting agents has been poorly investigated. The aim of this study was the characterisation of a collection of 69 yeast strains isolated from Spanish vineyards. Phytobeneficial attributes such as solubilisation of nutrients, synthesis of active biomolecules and cell wall-degrading enzyme production were analysed. Strains that revealed multiple growth-promoting characteristics were identified. The in vitro co-culture of Nicotiana benthamiana with yeast isolates showed enhancement of plant growth in 10 strains (up to 5-fold higher shoot dry weight in the case of Hyphopichia pseudoburtonii Hp-54), indicating a beneficial direct yeast-plant interaction. In addition, 18 out of the 69 strains increased dry weight and the number of roots per seedling when tobacco seeds were inoculated. Two of these, Pichia dianae Pd-2 and Meyerozyma guilliermondii Mg-11, also increased the chlorophyll content. The results in tobacco were mostly reproduced in lettuce with these two strains, which demonstrates that the effect of the yeast-plant interaction is not species-specific. In addition, the yeast collection was evaluated in maize seedlings grown in soil in a phytotron. Three isolates (Debaryomyces hansenii Dh-67, Lachancea thermotolerans Lt-69 and Saccharomyces cerevisiae Sc-6) promoted seedling development (increases of 10 % in dry weight and chlorophyll content). In conclusion, our data confirm that several yeast strains can promote plant growth and could be considered for the development of biological fertiliser treatments.

[Quantitative gait analysis in patients with advanced Parkinson's disease]. / Analisis cuantitativo de la marcha en pacientes con enfermedad de Parkinson avanzada.

AIM: To describe the gait disorders and postural instability in a group of patients with advanced Parkinson's disease (PD). PATIENTS AND METHODS: Gait was analysed in patients in advanced stages of PD on medication. Using a computerised analysis system, we studied the kinematic variables: cadence, number of correct gait cycles (HFPS cycles), total number of cycles, duration of the phases of the cycle, electromyography and a goniometric study of the knee and the ankle. The clinical appraisal of balance and postural instability was completed with the Tinetti and Timed Up and Go tests. RESULTS: The analysis showed alterations in the spatio-temporal parameters with respect to the ranges considered to be normal: reduction of the HFPS cycles, increase in the total number of cycles and alteration of the cadence in many patients. It also revealed that the mean cadence was kept within the limits of normal values, an increase in the duration of the contact phase, reduction of monopodal support and alteration of the joint range of motion of the knee and the ankle. Likewise, changes are also observed in the scores obtained on the clinical scales, which show an increase in the risk factor for falls and mild dependence. CONCLUSION: Quantification by objective analysis of the kinetic and kinematic variables in patients with PD can be used as a tool to establish the influence of the different therapeutic alternatives in gait disorders.

TITLE: Analisis cuantitativo de la marcha en pacientes con enfermedad de Parkinson avanzada.Objetivo. Describir las alteraciones de la marcha e inestabilidad postural en un grupo de pacientes con enfermedad de Parkinson (EP) avanzada. Pacientes y metodos. Se analizo la marcha de pacientes con EP en estadio avanzado on medicacion. Por medio de un sistema de analisis computarizado del movimiento, se estudiaron las variables cinematicas: cadencia, numero de ciclos con apoyo correcto (ciclos HFPS), numero de ciclos totales, duracion de las fases del ciclo, electromiografia, y goniometria de rodilla y tobillo. La valoracion clinica del equilibrio y la inestabilidad postural se completo con los tests Tinetti y Timed Up and Go. Resultados. El analisis mostro alteraciones en los parametros espaciotemporales con respecto a los rangos de normalidad: disminucion de los ciclos HFPS, aumento del numero total de ciclos y alteracion de la cadencia en muchos pacientes, y conservacion de la cadencia media dentro de los limites de la normalidad, aumento de la duracion de la fase de apoyo, disminucion del apoyo monopodal y alteracion del rango articular de la rodilla y el tobillo. Asimismo, se observo una alteracion en las puntuaciones obtenidas en las escalas clinicas, que mostraban un aumento del factor de riesgo de caidas y dependencia leve. Conclusion. La cuantificacion mediante analisis objetivo de las variables cineticas y cinematicas en los pacientes con EP puede emplearse como herramienta para establecer la influencia de las distintas alternativas terapeuticas en el trastorno de la marcha.

Positive selection and compensatory adaptation interact to stabilize non-transmissible plasmids.

Plasmids are important drivers of bacterial evolution, but it is challenging to understand how plasmids persist over the long term because plasmid carriage is costly. Classical models predict that horizontal transfer is necessary for plasmid persistence, but recent work shows that almost half of plasmids are non-transmissible. Here we use a combination of mathematical modelling and experimental evolution to investigate how a costly, non-transmissible plasmid, pNUK73, can be maintained in populations of Pseudomonas aeruginosa. Compensatory adaptation increases plasmid stability by eliminating the cost of plasmid carriage. However, positive selection for plasmid-encoded antibiotic resistance is required to maintain the plasmid by offsetting reductions in plasmid frequency due to segregational loss. Crucially, we show that compensatory adaptation and positive selection reinforce each other's effects. Our study provides a new understanding of how plasmids persist in bacterial populations, and it helps to explain why resistance can be maintained after antibiotic use is stopped.