Topological digestion drives time-varying rheology of entangled DNA fluids.

Understanding and controlling the rheology of polymeric complex fluids that are pushed out-of-equilibrium is a fundamental problem in both industry and biology. For example, to package, repair, and replicate DNA, cells use enzymes to constantly manipulate DNA topology, length, and structure. Inspired by this feat, here we engineer and study DNA-based complex fluids that undergo enzymatically-driven topological and architectural alterations via restriction endonuclease (RE) reactions. We show that these systems display time-dependent rheological properties that depend on the concentrations and properties of the comprising DNA and REs. Through time-resolved microrheology experiments and Brownian Dynamics simulations, we show that conversion of supercoiled to linear DNA topology leads to a monotonic increase in viscosity. On the other hand, the viscosity of entangled linear DNA undergoing fragmentation displays a universal decrease that we rationalise using living polymer theory. Finally, to showcase the tunability of these behaviours, we design a DNA fluid that exhibits a time-dependent increase, followed by a temporally-gated decrease, of its viscosity. Our results present a class of polymeric fluids that leverage naturally occurring enzymes to drive diverse time-varying rheology by performing architectural alterations to the constituents.

Evaluación del perfil de seguridad del medicamento lopinavir/ritonavir (Lpv/r) en los pacientes sospechosos o confirmados por COVID-19 / Evaluation of the safety profile of the drug lopinavir/ritonavir (Lpv/r) in suspected or confirmed COVID-19 patients

Introducción: El nuevo SARS-CoV-2, es el agente causal de la enfermedad COVID-19. La Organización Mundial de la Salud (OMS) ha referenciado el uso del lopinavir/ritonavir (Lpv/r), es un inhibidor de la proteasa del virus de inmunodeficiencia humana adquirida (VIH-1). El estudio clínico de Cao et al., identificó que el uso de Lpv/r no se asociaron con un mayor número de eventos adversos en comparación con el tratamiento estándar.Materiales y métodos: Estudio retrospectivo de farmacovigilancia en una cohorte en pacientes sospechosos o confirmados de COVID-19 en un hospital de tercer Nivel de la Ciudad de México en el periodo 01 abril 2020 al 30 julio 2020. Resultados: El tratamiento de Lpv/r incluyó 140 pacientes, de los cuales 91 pacientes completaron el tratamiento, mientras que 50 pacientes no terminaron el esquema. Los principales motivos de la suspensión del esquema del medicamento fueron: alta por mejoría (11 casos), defunciones (10 casos) y por inicio de ruxolitinib (9 casos). Además, se identificaron 8 reacciones adversas al medicamento, de las cuales 5 son reacciones asociadas a los trastornos gastrointestinales (diarreas) y las otras 3 reacciones asociadas a trastornos hepatobiliares (hipertransaminasemia).Conclusión: El perfil de seguridad del medicamento Lpv/r demostró una coherencia con las observaciones de estudios previos en relación en los eventos adversos presentados de tipo gastrointestinales y hepáticos, estos últimos se encuentran relacionados a interacción fármaco-fármaco, por lo que sugerimos un seguimiento farmacoterapéutico para identificar las interacciones y las reacciones adversas durante el uso Lpv/r. (AU)

Abstract: The new SARS-CoV-2 is the causal agent for COVID-19. The World Health Organization (WHO) referenced the use of lopinavir/ritonavir (Lpv/r), which is a protease inhibitor of human inmunodeficiency virus (HIV-1). The Clinical trial by Cao et al. identified that the use of Lpv/r has not been associated with any increase of adverse drug reactions within compared to the standard of care.Materials and methods: Pharmacovigilance retrospective study of patients suspected or confirmed with COVID-19 in a 3rd level hospital in Mexico City from April, 01 2020 to July, 30 2020.Results: Lopinavir/ritonavir treatment was prescribed 140 patients from which 91 patients completed the treatment, while 50 patients did not completed the treatment. The cause suspensions were: patient discharge for improvement (11 cases), deaths (10 cases) and start of ruxolitinib (9 cases). In addition, were identify 8 adverse drug reaction from which 5 were associated to gastrointestinal disorders (diarrhea) and 3 hepatobiliary disorders (hypertransaminasemia).Conclusion: The safety profile of the Lpv/r demonstrated consistency with the observations of previous studies in relation to gastrointestinal and hepatic adverse events, which were related to drug-drug interaction, so we suggest a pharmacotherapeutic monitoring to identify them as well as adverse drug reactions due to Lpv/r. (AU)

Exposing a dynamical signature of the freezing transition through the sound propagation gap.

The conventional view of freezing holds that nuclei of the crystal phase form in the metastable fluid through purely stochastic thermal density fluctuations. The possibility of a change in the character of the fluctuations as the freezing point is traversed is beyond the scope of this perspective. Here we show that this perspective may be incomplete by examination of the time autocorrelation function of the longitudinal current, computed by molecular dynamics for the hard-sphere fluid around its freezing point. In the spatial window where sound is overdamped, we identify a change in the long-time decay of the correlation function at the known freezing points of monodisperse and moderately polydisperse systems. The fact that these findings agree with previous experimental studies of colloidal systems in which particle are subject to diffusive dynamics, suggests that the dynamical signature we identify with the freezing transition is a consequence of packing effects alone.

Switching of Swimming Modes in Magnetospirillium gryphiswaldense.

The microaerophilic magnetotactic bacterium Magnetospirillum gryphiswaldense swims along magnetic field lines using a single flagellum at each cell pole. It is believed that this magnetotactic behavior enables cells to seek optimal oxygen concentration with maximal efficiency. We analyze the trajectories of swimming M. gryphiswaldense cells in external magnetic fields larger than the earth's field, and show that each cell can switch very rapidly (in <0.2 s) between a fast and a slow swimming mode. Close to a glass surface, a variety of trajectories were observed, from straight swimming that systematically deviates from field lines to various helices. A model in which fast (slow) swimming is solely due to the rotation of the trailing (leading) flagellum can account for these observations. We determined the magnetic moment of this bacterium using a to our knowledge new method, and obtained a value of (2.0±0.6) × 10(-16) A · m(2). This value is found to be consistent with parameters emerging from quantitative fitting of trajectories to our model.

Filling an emulsion drop with motile bacteria.

We have measured the spatial distribution of motile Escherichia coli inside spherical water droplets emulsified in oil. At low cell concentrations, the cell density peaks at the water-oil interface; at increasing concentration, the bulk of each droplet fills up uniformly while the surface peak remains. Simulations and theory show that the bulk density results from a "traffic" of cells leaving the surface layer, increasingly due to cell-cell scattering as the surface coverage rises above ∼10%. Our findings show similarities with the physics of a rarefied gas in a spherical cavity with attractive walls.

Dynamics of hard sphere suspensions using dynamic light scattering and X-ray photon correlation spectroscopy: dynamics and scaling of the intermediate scattering function.

Intermediate scattering functions are measured for colloidal hard sphere systems using both dynamic light scattering and x-ray photon correlation spectroscopy. We compare the techniques, and discuss the advantages and disadvantages of each. Both techniques agree in the overlapping range of scattering vectors. We investigate the scaling behavior found by Segré and Pusey [Phys. Rev. Lett. 77, 771 (1996)] but challenged by Lurio et al. [Phys. Rev. Lett. 84, 785 (2000)]. We observe a scaling behavior over several decades in time but not in the long-time regime. Moreover, we do not observe long-time diffusive regimes at scattering vectors away from the peak of the structure factor and so question the existence of long-time diffusion coefficients at these scattering vectors.

Differential dynamic microscopy of bacterial motility.

We demonstrate a method for the fast, high-throughput characterization of the dynamics of active particles. Specifically, we measure the swimming speed distribution and motile cell fraction in Escherichia coli suspensions. By averaging over ∼10(4) cells, our method is highly accurate compared to conventional tracking, yielding a routine tool for motility characterization. We find that the diffusivity of nonmotile cells is enhanced in proportion to the concentration of motile cells.

Aging dynamics of colloidal hard sphere glasses.

We report the results of dynamic light scattering measurements of the coherent intermediate scattering function (ISF) of glasses of colloidal hard spheres for several volume fractions and a range of scattering vectors around the primary peak of the static structure factor. The ISF shows a clear crossover from an initial fast decay to a slower nonstationary decay. Aging is quantified in several different ways. However, regardless of the method chosen, the perfect "aged" glass is approached in a power law fashion. In particular the coupling between the fast and slow decays, as measured by the degree of stretching of the ISF at the crossover, also decreases algebraically with waiting time. The nonstationarity of this coupling implies that even the fastest detectable processes are themselves nonstationary.

Arrest of flow and emergence of activated processes at the glass transition of a suspension of particles with hard spherelike interactions.

By combining aspects of the coherent and self-intermediate scattering functions, we show that the arrest of particle number density fluctuations spreads from the position of the main structure factor peak. We propose that this arrest impairs the system's ability to respond to diffusing momentum currents, leading to an enhanced resistance to flow. From the stretching of the coherent intermediate scattering functions in the glass, we read a manifestation of the undissipated thermal energy-the source of the ergodicity restoring processes that short-circuit the sharp transition to a perfect glass.

Scaling of the space-time correlation function of particle currents in a suspension of hard-sphere-like particles: exposing when the motion of particles is Brownian.

The current correlation function is determined from dynamic light scattering measurements of a suspension of particles with hard spherelike interactions. For suspensions in thermodynamic equilibrium we find scaling of the space and time variables of the current correlation function. This finding supports the notion that the movement of suspended particles can be described in terms of uncorrelated Brownian encounters. However, in the metastable fluid, at volume fractions above freezing, this scaling fails.

Slow dynamics and aging of a colloidal hard sphere glass.

The intermediate scattering function (ISF) is measured for a colloidal hard-sphere glass as functions of the scattering vector and waiting time. For scattering vectors near the structure factor peak, we show that the ISF and the stretching index, defined at the crossover time between the fast and slow processes, depend algebraically on the waiting time. By contrast, the Debye-Waller factor is independent of the waiting time.

On the use of double haploids for detecting QTL in outbred populations.

The power to detect quantitative trait loci (QTL) using the double haploid (DH), full-sib (FS) and hierarchical (HI) designs implemented in outbred fish populations was assessed for interval mapping using deterministic methods. The predictions were tested using simulation. The DH design was most efficient for the range of designs and parameters considered and was most beneficial when the FS design was not very powerful. The difference between the design was largest for a low amount of residual genetic variation. Accounting for an increase of the environmental variance due to the genetic constitution of the double haploid progeny changed the magnitude of the power, but the ranking of the designs remained the same. As large full sib family sizes can be obtained in fish, the practical value of HI designs as a strategy for increasing the power of QTL mapping experiments is limited when compared with the FS design. Overall, the results suggested that the DH design could be a very useful tool for QTL mapping in fish, and of particular importance when the effect of the QTL is low and the residual genetic variation from other chromosomes can be controlled by using multiple markers.