Large-scale microtubule networks contract quite well.

The quantitative investigation of how networks of microtubules contract can boost our understanding of actin biology

A theory that predicts behaviors of disordered cytoskeletal networks.

Morphogenesis in animal tissues is largely driven by actomyosin networks, through tensions generated by an active contractile process. Although the network components and their properties are known, and networks can be reconstituted in vitro, the requirements for contractility are still poorly understood. Here, we describe a theory that predicts whether an isotropic network will contract, expand, or conserve its dimensions. This analytical theory correctly predicts the behavior of simulated networks, consisting of filaments with varying combinations of connectors, and reveals conditions under which networks of rigid filaments are either contractile or expansile. Our results suggest that pulsatility is an intrinsic behavior of contractile networks if the filaments are not stable but turn over. The theory offers a unifying framework to think about mechanisms of contractions or expansion. It provides the foundation for studying a broad range of processes involving cytoskeletal networks and a basis for designing synthetic networks

Instantaneous cell migration velocity may be ill-defined

Cell crawling is critical to biological development, homeostasis and disease. In many cases, cell trajectories are quasi-random-walk. In vitro assays on flat surfaces often described such quasi-random-walk cell trajectories as approximations to a solution of a Langevin process. However, experiments show quasi-diffusive behavior at small timescales, indicating that instantaneous velocity and velocity autocorrelations are not well-defined. We propose to characterize mean-squared cell displacement using a modified F\"urth equation with three temporal and spatial regimes: short- and long-time/range diffusion and intermediate time/range ballistic motion. This analysis collapses mean-squared displacements of previously published experimental data onto a single-parameter family of curves, allowing direct comparison between movement in different cell types, and between experiments and numerical simulations. Our method also show that robust cell-motility quantification requires an experiment with a maximum interval between images of a few percent of the cell-motion persistence time or less, and a duration of a few orders-of-magnitude longer than the cell-motion persistence time or more.Comment: 5 pages, plus Supplemental materia

A disassembly-driven mechanism explains F-actin-mediated chromosome transport in starfish oocytes.

While contraction of sarcomeric actomyosin assemblies is well understood, this is not the case for disordered networks of actin filaments (F-actin) driving diverse essential processes in animal cells. For example, at the onset of meiosis in starfish oocytes a contractile F-actin network forms in the nuclear region transporting embedded chromosomes to the assembling microtubule spindle. Here, we addressed the mechanism driving contraction of this 3D disordered F-actin network by comparing quantitative observations to computational models. We analyzed 3D chromosome trajectories and imaged filament dynamics to monitor network behavior under various physical and chemical perturbations. We found no evidence of myosin activity driving network contractility. Instead, our observations are well explained by models based on a disassembly-driven contractile mechanism. We reconstitute this disassembly-based contractile system in silico revealing a simple architecture that robustly drives chromosome transport to prevent aneuploidy in the large oocyte, a prerequisite for normal embryonic development

Micafungin as antifungal prophylaxis in non-transplanted haemotological patients

Introduction. Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocandins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efficacy and safety of micafungin in the antifungal prophylaxis of haematological patients on chemotherapy. Material and methods. A multicentre, observational retrospective study was performed in 7 Haematology Departments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included. Results. There were 5 cases of probable or proven fungal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 aspergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity. Conclusion. Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efficacy and an excellent toxicity profile, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode

Virtual-tissue computer simulations define the roles of cell adhesion and proliferation in the onset of kidney cystic disease

In autosomal dominant polycystic kidney disease (ADPKD), cysts accumulate and progressively impair renal function. Mutations in PKD1 and PKD2 genes are causally linked to ADPKD, but how these mutations drive cell behaviors that underlie ADPKD pathogenesis is unknown. Human ADPKD cysts frequently express cadherin-8 (cad8), and expression of cad8 ectopically in vitro suffices to initiate cystogenesis. To explore cell behavioral mechanisms of cad8-driven cyst initiation, we developed a virtual-tissue computer model. Our simulations predicted that either reduced cell-cell adhesion or reduced contact inhibition of proliferation triggers cyst induction. To reproduce the full range of cyst morphologies observed in vivo, changes in both cell adhesion and proliferation are required. However, only loss-of-adhesion simulations produced morphologies matching in vitro cad8-induced cysts. Conversely, the saccular cysts described by others arise predominantly by decreased contact inhibition, that is, increased proliferation. In vitro experiments confirmed that cell-cell adhesion was reduced and proliferation was increased by ectopic cad8 expression. We conclude that adhesion loss due to cadherin type switching in ADPKD suffices to drive cystogenesis. Thus, control of cadherin type switching provides a new target for therapeutic intervention

Deterioro cognitivo posquirúrgico a largo plaza tras cirugía cardiaca

Objetivos: Evaluar de forma longitudinal el Deterioro Cognitivo Postquirúrgico (DCP) a largo plazo en pacientes tras cirugía cardíaca, analizar el perfil cognitivo obtenido e identificar los factores de riesgo involucrados. Material y Métodos: Estudio prospectivo de 70 pacientes sometidos a cirugía cardíaca (36 con……..). Se recogieron los datos sociodemográficos y clínicos y se realizó evaluación longitudinal neuropsicológica (pre y postquirúrgica a los 1, 6 y 12 meses) para caracterizar el DCP (Proyecto Neuronorma). Se evaluaron las funciones ejecutivas (Test del Trazo, Test de Stroop), memoria (Test de Recuerdo libre y selectivamente facilitado), fluidez verbal (Semántica y Fonológica) y función visuoespacial (Orientación de Líneas. Se valoró también depresión y ansiedad (escalas de Hamilton). Resultados: Se comprobó la presencia de DCP en los dos grupos de pacientes (p>0.05-p>0.001, mayor en el grupo con CEC), que fue máximo a los 6 meses de la intervención, pero aún significativo a los 12 meses. El deterioro cognitivo se asoció con variables intraoperatorias (baja saturación de oxígeno intraoperatoria y tiempo de bypass cardiopulmonar prolongado) y con factores de riesgo cardiovasculares (tabaquismo, insuficiencia cardíaca, hipertrofia ventricular izquierda, diabetes mellitus, enfermedad coronaria de 3 vasos y arteriopatía periférica) como factores predictivos. Conclusión: Los resultados indican la prevalencia del deterioro cognitivo postquirúrgico (DCP) al año de la intervención en ambos grupos, siendo mayor en el grupo con CEC. El DCP se caracteriza por un deterioro multidominio significativo en atención, funciones ejecutivas y fluencia verbal. Se describen los factores intraoperatorios y cardiovasculares significativos en el DCP, planteando la necesidad de establecer protocolos para su detección así como su prevención.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation

Somitogenesis, the formation of the body's primary segmental structure common to all vertebrate development, requires coordination between biological mechanisms at several scales. Explaining how these mechanisms interact across scales and how events are coordinated in space and time is necessary for a complete understanding of somitogenesis and its evolutionary flexibility. So far, mechanisms of somitogenesis have been studied independently. To test the consistency, integrability and combined explanatory power of current prevailing hypotheses, we built an integrated clock-and-wavefront model including submodels of the intracellular segmentation clock, intercellular segmentation-clock coupling via Delta/Notch signaling, an FGF8 determination front, delayed differentiation, clock-wavefront readout, and differential-cell-cell-adhesion-driven cell sorting. We identify inconsistencies between existing submodels and gaps in the current understanding of somitogenesis mechanisms, and propose novel submodels and extensions of existing submodels where necessary. For reasonable initial conditions, 2D simulations of our model robustly generate spatially and temporally regular somites, realistic dynamic morphologies and spontaneous emergence of anterior-traveling stripes of Lfng. We show that these traveling stripes are pseudo-waves rather than true propagating waves. Our model is flexible enough to generate interspecies-like variation in somite size in response to changes in the PSM growth rate and segmentation-clock period, and in the number and width of Lfng stripes in response to changes in the PSM growth rate, segmentation-clock period and PSM length

A disassembly-driven mechanism explains F-actin-mediated chromosome transport in starfish oocytes.

While contraction of sarcomeric actomyosin assemblies is well understood, this is not the case for disordered networks of actin filaments (F-actin) driving diverse essential processes in animal cells. For example, at the onset of meiosis in starfish oocytes a contractile F-actin network forms in the nuclear region transporting embedded chromosomes to the assembling microtubule spindle. Here, we addressed the mechanism driving contraction of this 3D disordered F-actin network by comparing quantitative observations to computational models. We analyzed 3D chromosome trajectories and imaged filament dynamics to monitor network behavior under various physical and chemical perturbations. We found no evidence of myosin activity driving network contractility. Instead, our observations are well explained by models based on a disassembly-driven contractile mechanism. We reconstitute this disassembly-based contractile system in silico revealing a simple architecture that robustly drives chromosome transport to prevent aneuploidy in the large oocyte, a prerequisite for normal embryonic development