A Yap-dependent mechano-regulatory loop directs cell migration for embryo axis assembly

Programa de Doctorado en Biotecnología, Ingeniería y Tecnología QuímicaLínea de Investigación: Biología del DesarrolloClave Programa: DBICódigo Línea: 107Gastrulation is a decisive process that occurs during embryonic development, in which a relatively homogenous group of cells is transformed into an embryo with established body axes and presenting the three germ layers. This is achieved through complex cell rearrangements that are tightly controlled by the interplay of the different types of morphogenetic inputs. In the animal kingdom, striking divergences exist in embryonic development, as they evolve and adapt to different environments, egg architecture and speed of development. However, even though large differences can be found among the different species, the underlying logic and principles governing the gastrulation movements are conserved. The set of cell movements observed during gastrulation is not exclusive to this process, as they are also generally involved in organogenesis, tissue regeneration, and cancer progression. Therefore, understanding how the gastrulation movements are coordinated and controlled is essential not only to understand axis formation, but also how tissues and organs are build, and even which are the mechanism underlying oncogenic growth and metastasis. The key role of mechanical inputs during tissue morphogenesis is becoming increasingly evident, however little is known about how these inputs shape and regulate gastrulation. Among the most well-known transcriptional activators that cells use to interpret mechanical signals are YAP proteins, yet their role in gastrulation remains elusive. Our detailed analysis of yap1 and yap1b double mutants in medaka fish shows that these mechanosensors are required for the assembly of the primary embryo axis: a key event for the establishment of the vertebrate body plan. Using quantitative imaging and live-sensors, we show that Yap activity is required for the proper migration of dorsally converging cells towards the embryo midline. Thus, mutant cells display reduced velocity and migratory persistence resulting in shorter cell displacements in many cases insufficient to reach the midline. Combining RNA-seq with previous DamID-seq data, we characterize the transcriptional program directly activated by Yap proteins, which mostly entails the recruitment of actin cytoskeleton regulators, ECM molecules and focal adhesion components. Moreover, we show that Yap activation depends itself on intracellular tension, closing a positive feedback loop that maintains directed cell migration.Universidad Pablo de Olavide de Sevilla. Departamento de Biología Molecular e Ingeniería Bioquímic

Hematoma subdural como complicación de analgesia epidural de parto. A propósito de dos casos

Las hemorragias intracraneales son una complicación infrecuente pero potencialmente grave tras la punción dural asociada a anestesia neuroaxial. Las consecuencias pueden ser catastróficas, especialmente cuando hablamos de anestesia neuroaxial obstétrica en mujeres jóvenes y sanas. El diagnóstico puede ser difícil por la similitud de síntomas con la cefalea postpunción dural (CPPD), que es la complicación más frecuente tras una punción dural. Este trabajo tiene como objetivo, aumentar la conciencia de los profesionales ante la posibilidad de ocurrencia de este tipo de complicaciones ante una punción dural accidental.  ABSTRACT Intracranial hemorrhages are a rare but potentially serious complication following dural puncture associated with neuraxial anesthesia. The consequences can be catastrophic, especially when we talk about neuraxial obstetric anesthesia in young and healthy women. Dagnosis may be difficult due to the similarity of symptoms between these and post-dural puncture headache, which is the most frequent complication after a dural puncture. This work aims to increase the awareness of professionals for the possibility of occurrence of this type of complications when an accidental dural puncture has occured

Hematoma subdural como complicación de analgesia epidural de parto. A propósito de dos casos

Intracranial hemorrhages are a rare but potentially serious complication following dural puncture associated with neuraxial anesthesia. The consequences can be catastrophic, especially when we talk about neuraxial obstetric anesthesia in young and healthy women. Dagnosis may be difficult due to the similarity of symptoms between these and post-dural puncture headache, which is the most frequent complication after a dural puncture. This work aims to increase the awareness of professionals for the possibility of occurrence of this type of complications when an accidental dural puncture has occured.Las hemorragias intracraneales son una complicación infrecuente pero potencialmente grave tras la punción dural asociada a anestesia neuroaxial. Las consecuencias pueden ser catastróficas, especialmente cuando hablamos de anestesia neuroaxial obstétrica en mujeres jóvenes y sanas. El diagnóstico puede ser difícil por la similitud de síntomas con la cefalea postpunción dural (CPPD), que es la complicación más frecuente tras una punción dural. Este trabajo tiene como objetivo, aumentar la conciencia de los profesionales ante la posibilidad de ocurrencia de este tipo de complicaciones ante una punción dural accidental.

A Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly

The assembly of the embryo’s primary axis is a fundamental landmark for the establishment of the vertebrate body plan. Although the morphogenetic movements directing cell convergence towards the midline have been described extensively, little is known on how gastrulating cells interpret mechanical cues. Yap proteins are well-known transcriptional mechanotransducers, yet their role in gastrulation remains elusive. Here we show that the double knockout of yap and its paralog yap1b in medaka results in an axis assembly failure, due to reduced displacement and migratory persistence in mutant cells. Accordingly, we identified genes involved in cytoskeletal organization and cell-ECM adhesion as potentially direct Yap targets. Dynamic analysis of live sensors and downstream targets reveal that Yap is acting in migratory cells, promoting cortical actin and focal adhesions recruitment. Our results indicate that Yap coordinates a mechanoregulatory program to sustain intracellular tension and maintain the directed cell migration for embryo axis development

Modeling emergence of sterile oat (Avena sterilis ssp. ludoviciana) under semiarid conditions

Winter wild oat [Avena sterilisssp. ludoviciana (Durieu) Gillet & Magne; referred to as A. sterilis here] is one of the major weed species of the Avena genus, given its high competitive ability to infest cereal crops worldwide, with special concern in Spain. A nine-location field experiment was established across Spain where a total of 400 A. sterilis seeds per location were sowed in four replicates in autumn 2016 to monitor the emergence during two growing seasons in dryland conditions. The data were used to test the prediction ability of previously published thermal (TT) and hydrothermal time (HTT) models and to develop new models, if required. Overall, the average percentage of emergence was 30% during the first season and 21% during the second season. In both seasons, the main emergence flush occurred between November and February. According to the phenological stage, A. sterilis achieved the tillering earlier in southern sites, between November 25 and the end of December, compared with northern sites, where this stage was reached at the end of January. The newly developed model described the emergence with precision, using three cardinal temperatures to estimate the TT. The three car dinal points were established at −1.0, 5.8, and 18.0 C for base (Tb), optimum (To), and ceiling temperature (Tc), while the base water potential (Ψb) was established at −0.2 MPa for the HTT estimation. This study contributes to improving prediction of the emergence of A. sterilis and provides knowledge for decision support systems (DSS) for the control of this weed.We would like to thank first the funding institutions, Cátedra Adama and the Spanish Weed Science Society (SEMh), with special mention of Cátedra Adama, which financed the article publishing charges. Also, JT acknowledges support from the Spanish Ministry of Science, Innovation and Universities (grant Ramon y Cajal RYC2018-023866-I). We also want to thank the students and the technicians that have helped with the fieldwork for this experiment in different sites, without whose help data col lection would have been more difficult. No conflicts of interest have been declared

Should emergence models for Lolium rigidum be changed throughout climatic conditions? The case of Spain

Lolium rigidum Gaudin is a troublesome weed worldwide, and its distribution may increase due to climate change. It has become resistant to several herbicides and, therefore, its control is problematic. On the other hand, its seed biology, with little dormancy and short-term viability, can play a major role in reducing its seed bank, which would improve control of this weed. For this reason, knowledge of the emergence patterns of this species entails improvements for its management. In this work seeds from one population of L. rigidum, collected in Northeastern Spain, were distributed and sown in 11 sites across Spain, and its emergence was followed every 2–7 days for two growing seasons (2016-17 and 2017–18). These emergence sequences were compared with previously published thermal time and hydrothermal time based models, and new models were developed afterwards. The hydrothermal time based model did not significantly improve models based solely on thermal time. The accuracy of these newly developed models varied from site to site, but in general, they worked better for Northern locations than for Southern locations. Thus, the experimental sites were split between North and South, and specific models for each region were developed. The model developed for Northern sites worked very well, but the one for Southern sites needs improvement. This works reveals that, with regard to this weed species, probably different models should be developed for different climatic conditions. The model developed with data from Northern sites should be validated with local populations, while the one developed with data from Southern sites will probably need to be revised or newly developed with data from more Southern populations.The group from the University of Lleida-Agrotecnio would also like to thank the Spanish Goverment for partial funding, through project AGL2017-83325-C4-2-R (AEI/FEDER/UE)

Mutation of vsx genes in zebrafish highlights the robustness of the retinal specification network

Genetic studies in human and mice have established a dual role for Vsx genes in retina development: an early function in progenitors' specification, and a later requirement for bipolar-cells fate determination. Despite their conserved expression patterns, it is currently unclear to which extent Vsx functions are also conserved across vertebrates, as mutant models are available only in mammals. To gain insight into vsx function in teleosts, we have generated vsx1 and vsx2 CRISPR/Cas9 double knockouts (vsxKO) in zebrafish. Our electrophysiological and histological analyses indicate severe visual impairment and bipolar cells depletion in vsxKO larvae, with retinal precursors being rerouted toward photoreceptor or Müller glia fates. Surprisingly, neural retina is properly specified and maintained in mutant embryos, which do not display microphthalmia. We show that although important cis-regulatory remodelling occurs in vsxKO retinas during early specification, this has little impact at a transcriptomic level. Our observations point to genetic redundancy as an important mechanism sustaining the integrity of the retinal specification network, and to Vsx genes regulatory weight varying substantially among vertebrate species

The convolutional neural network as a tool to classify electroencephalography data resulting from the consumption of juice sweetened with caloric or non-caloric sweeteners

Sweetener type can influence sensory properties and consumer’s acceptance and preference for low-calorie products. An ideal sweetener does not exist, and each sweetener must be used in situations to which it is best suited. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice. Despite the interest in artificial sweeteners, little is known about how artificial sweeteners are processed in the human brain. Here, we applied the convolutional neural network (CNN) to evaluate brain signals of 11 healthy subjects when they tasted passion fruit juice equivalently sweetened with sucrose (9.4 g/100 g), sucralose (0.01593 g/100 g), or aspartame (0.05477 g/100 g). Electroencephalograms were recorded for two sites in the gustatory cortex (i.e., C3 and C4). Data with artifacts were disregarded, and the artifact-free data were used to feed a Deep Neural Network with tree branches that applied a Convolutions and pooling for different feature filtering and selection. The CNN received raw signal as input for multiclass classification and with supervised training was able to extract underling features and patterns from the signal with better performance than handcrafted filters like FFT. Our results indicated that CNN is an useful tool for electroencephalography (EEG) analyses and classification of perceptually similar tastes

Modeling the emergence of North African knapweed (Centaurea diluta), an increasingly troublesome weed in Spain

10 Pág.North African knapweed (Centaurea diluta Aiton) is an annual weed that is widespread in southern Spain and is of increasing concern in dryland cropping systems. Despite its expanding range in Spain, there is limited information on the emergence timing and pattern of this species, knowledge of which is critical for developing more timely and effective management strategies. Therefore, there is a need to develop simple and reliable models to predict the timing and emergence of this annual weed under dryland conditions. A multi-location field experiment was established across Spain in 2016 to 2017 to assess the emergence of C. diluta. At each of 11 locations, seeds were sown in the fall, and emergence was recorded. Overall emergence averaged 39% in the first year across all sites and 11% in the second year. In both years, the main emergence flush occurred at the beginning of the growing season. A three-parameter Weibull function best described seedling emergence of C. diluta. Emergence models were developed based on thermal time (TT) and hydrothermal time (HTT) and showed high predictability, as evidenced by root mean-square error prediction values of 10.8 and 10.7, respectively. Three cardinal points were established for TT and HHT at 0.5, 10, and 35 C for base, optimal, and ceiling temperatures, respectively, while base water potential was estimated at-0.5 MPa.We would like to thank Cátedra Adama and the Spanish Weed Science Society (SEMh) for providing financial support for this project. We are grateful to the many students and technicians who assisted with fieldwork at the different experimental locations. We would like to thank the Spanish government for partial funding, through project AVA 2019.020 “Advances in Technological Research in Winter Cereals: Genetic Improvement and Sustainable Management,” financed with Fondo Europeo de Desarrollo Regional (FEDER) funds (80%). Also, JT acknowledges support from the Spanish Ministry of Science, Innovation and Universities (grant Ramon y Cajal RYC2018-023866-I). We thank Enrique Chamber for installing and maintaining the data loggers at the various locations. No conflicts of interest have been declared.Peer reviewe