Stem Cells for Modeling Human Disease

Human pluripotent stem cells (PSCs) in the form of human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) are capable of growing indefinitely in vitro, maintaining their capacity to differentiate into the three primary germ layers: mesoderm, endoderm and ectoderm. Different protocols have been developed to differentiate PSCs into almost any cellular type with different degree of success. This technology has allowed scientists to use patient‐derived iPSCs to study the physiopathology of the disease by analyzing the phenotype of the cells derived from these iPSCs. However, control iPSCs obtained from healthy individuals will always have different genomic environment than patient\u27s iPSCs, making it difficult the interpretation of the cells phenotype. The recent appearance of specific nucleases [zinc‐finger nucleases (ZFNs), the transcription activator‐like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)] has made it possible to edit the genome of PSCs. We can now generate syngeneic hESCs or iPSCs harboring the desired mutation and comparing the emerging cells with those derived from genetically identical PSCs that will differ only in the mutated gene. In this chapter, we summarize the progress made in this field and discuss the different approaches that have been used recently for the generation of syngeneic human pluripotent cellular models for different pathologies

Monetary rewards modulate inhibitory control

The ability to override a dominant response, often referred to as behavioral inhibition, is considered a key element of executive cognition. Poor behavioral inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioral inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/NoGo and Stop Signal Tasks (SSTs). Several studies have reported a positive modulatory effect of reward on performance in pathological conditions such as substance abuse, pathological gambling, and Attention Deficit Hyperactive Disorder (ADHD). However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory tasks are scarce and little is known about the finer grained relationship between motivation and inhibitory control. Here we probed the effect of reward magnitude and context on behavioral inhibition with three modified versions of the widely used SST. The pilot study compared inhibition performance during six blocks alternating neutral feedback, low, medium, and high monetary rewards. Study One compared increasing vs. decreasing rewards, with low, high rewards, and neutral feedback; whilst Study Two compared low and high reward magnitudes alone also in an increasing and decreasing reward design. The reward magnitude effect was not demonstrated in the pilot study, probably due to a learning effect induced by practice in this lengthy task. The reward effect per se was weak but the context (order of reward) was clearly suggested in Study One, and was particularly strongly confirmed in study two. In addition, these findings revealed a 'kick start effect' over global performance measures. Specifically, there was a long lasting improvement in performance throughout the task when participants received the highest reward magnitudes at the beginning of the protocol. These results demonstrate a dynamical behavioral inhibition capacity in humans, as illustrated by the reward magnitude modulation and initial reward history effects. © 2014 Herrera, Speranza, Hampshire and Bekinschtein

High-throughput analysis reveals novel maternal germline RNAs crucial for primordial germ cell preservation and proper migration

During oogenesis, hundreds of maternal RNAs are selectively localized to the animal or vegetal pole, including determinants of somatic and germline fates. Although microarray analysis has identified localized determinants, it is not comprehensive and is limited to known transcripts. Here, we utilized high-throughput RNA sequencing analysis to comprehensively interrogate animal and vegetal pole RNAs in the fully grown Xenopus laevis oocyte. We identified 411 (198 annotated) and 27 (15 annotated) enriched mRNAs at the vegetal and animal pole, respectively. Ninety were novel mRNAs over 4-fold enriched at the vegetal pole and six were over 10-fold enriched at the animal pole. Unlike mRNAs, microRNAs were not asymmetrically distributed. Whole-mount in situ hybridization confirmed that all 17 selected mRNAs were localized. Biological function and network analysis of vegetally enriched transcripts identified protein-modifying enzymes, receptors, ligands, RNA-binding proteins, transcription factors and co-factors with five defining hubs linking 47 genes in a network. Initial functional studies of maternal vegetally localized mRNAs show that sox7 plays a novel and important role in primordial germ cell (PGC) development and that ephrinB1 (efnb1) is required for proper PGC migration. We propose potential pathways operating at the vegetal pole that highlight where future investigations might be most fruitful.Fil: Owens, Dawn A.. University of Miami; Estados UnidosFil: Butler, Amanda M.. University of Miami; Estados UnidosFil: Agüero, Tristán Horacio. University of Miami; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Newman, Karen M.. University of Miami; Estados UnidosFil: Van Booven, Derek. University of Miami; Estados UnidosFil: King, Mary Lou. University of Miami; Estados Unido

BAP1 regulates epigenetic switch from pluripotency to differentiation in developmental lineages giving rise to BAP1-mutant cancers

The BAP1 tumor suppressor is mutated in many human cancers such as uveal melanoma, leading to poor patient outcome. It remains unclear how BAP1 functions in normal biology or how its loss promotes cancer progression. Here, we show that Bap1 is critical for commitment to ectoderm, mesoderm, and neural crest lineages during Xenopus laevis development. Bap1 loss causes transcriptional silencing and failure of H3K27ac to accumulate at promoters of key genes regulating pluripotency-to-commitment transition, similar to findings in uveal melanoma. The Bap1-deficient phenotype can be rescued with human BAP1, by pharmacologic inhibition of histone deacetylase (HDAC) activity or by specific knockdown of Hdac4. Similarly, BAP1-deficient uveal melanoma cells are preferentially vulnerable to HDAC4 depletion. These findings show that Bap1 regulates lineage commitment through H3K27ac-mediated transcriptional activation, at least in part, by modulation of Hdac4, and they provide insights into how BAP1 loss promotes cancer progression.Fil: Kuznetsov, Jeffim N.. University of Miami; Estados UnidosFil: Agüero, Tristán Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. University of Miami; Estados UnidosFil: Owens, Dawn A.. University of Miami; Estados UnidosFil: Kurtenbach, Stefan. University of Miami; Estados UnidosFil: Field, Matthew G.. University of Miami; Estados UnidosFil: Durante, Michael A.. University of Miami; Estados UnidosFil: Rodriguez, Daniel A.. University of Miami; Estados UnidosFil: King, Mary Lou. University of Miami; Estados UnidosFil: Harbour, J. William. University of Miami; Estados Unido

Compressed UAV sensing for flood monitoring by solving the continuous travelling salesman problem over hyperspectral maps

This is the final version. Available from SPIE via the DOI in this record.Remote Sensing of the Ocean, Sea Ice, Coastal Waters, and Large Water Regions 2018, 10 - 13 September 2018, Berlin, GermanyUnmanned Aerial Vehicles (UAVs) have shown great capability for disaster management due to their fast speed, automated deployment and low maintenance requirements. In recent years, disasters such as flooding are having increasingly damaging societal and environmental effects. To reduce their impact, real-time and reliable flood monitoring and prevention strategies are required. The limited battery life of small lightweight UAVs imposes efficient strategies to subsample the sensing field. This paper proposes a novel solution to maximise the number of inspected flooded cells while keeping the travelled distance bounded. Our proposal solves the so-called continuous Travelling Salesman Problem (TSP), where the costs of travelling from one cell to another depend not only on the distance, but also on the presence of water. To determine the optimal path between checkpoints, we employ the fast sweeping algorithm using a cost function defined from hyperspectral satellite maps identifying flooded regions. Preliminary results using MODIS flood maps show that our UAV planning strategy achieves a covered flooded surface approximately 4 times greater for the same travelled distance when compared to the conventional TSP solution. These results show new insights on the use of hyperspectral imagery acquired from UAVs to monitor water resourcesThis work was funded by the Royal Society of Edinburgh and National Science Foundation of China within the international project “Flood Detection and Monitoring using Hyperspectral Remote Sensing from Unmanned Aerial Vehicles” (project NNS/INT 15-16 Casaseca)

Inmediación a la cultura de la prevención y la comunicación en crisis, a través de sus responsables. Estudio de caso en San Luis Potosí, México

Think of crisis is not desirable for anyone imagined, because the crisis is instability and change, which creates uncertainty priority. Uncertainty which humans away because the smooth stable life is desirable, but in recent decades globalization and technological transformation are causing the change is incorporated as part of life and it is not an exception.Therefore it is necessary to know the concept of communication in general, the culture of prevention, and crisis communication in particular and the agents responsible for this government and educational consulting San Luis Potosi, Mexico are taken, for if exist or not a culture of prevention. To do this, focused on looking for a powerful exploratory interviews were used. The first results provide weak culture of prevention and crisis communication in the studied instances.Pensar en crisis no es un imaginario deseable para ninguna persona, porque la crisis supone inestabilidad y cambio, lo cual crea prioritariamente incertidumbre. Incertidumbre de la cual el ser humano se aleja porque la vida estable sin sobresaltos es lo deseable, pero en las últimas décadas la globalización y la tecnologización están provocando que el cambio se incorpore a la vida como parte de ella y no sea una excepción sino una realidad.Por ello se hace necesario conocer la concepción de la comunicación en general, la cultura de prevención, y la comunicación en crisis en particular, y para ello se toman los agentes responsables de instancias gubernamentales y educativas de San Luis Potosí, México, para conocer si existen o no una cultura de prevención. Para ello, se utilizaron entrevistas focalizadas en busca de un alcance exploratorio. Los primeros resultados aportan la debilidad de la cultura de prevención y comunicación en crisis en las instancias estudiadas

What to do in case of an endoscopic image of gastric necrosis or ischaemia post-funduplication? A case report

The association of gastric ischemia with a fundoplication is very rare and its management is not always surgical. The present paper describes the mechanism of post-fundoplication gastric ischemia that occurred in a patient diagnosed with gastroesophageal reflux disease treated with a Nissen-type gastric fundoplication. A clinical case of the Foregut Clinic of the Hospital General de Mexico (HGM) is presented. This is a 24-year-old patient undergoing a Nissen-type fundoplication who was discharged without eventualities and who presented intestinal occlusion, acute gastric dilation and gastric ischemia

Phase Equilibrium Properties of Binary and Ternary Mixtures Containing Dibutyl Ether, Cyclohexane, and Heptane or 1-Hexene at T = 313.15 K

New experimental isothermal P, x, y data for the ternary systems dibutyl ether + cyclohexane + heptane and dibutyl ether + cyclohexane + 1-hexene and for the binary systems dibutyl ether + 1-hexene and dibutyl ether + heptane at 313.15 K are reported. Data reduction by Barker’s method provides correlations for GE, using the Margules equation for the binary systems and the Wohl expansion for the ternary systems. Wilson, NRTL, and UNIQUAC models have been applied successfully to both of the binary and ternary mixtures presented here.Ministerio de Ciencia y Tecnología, Dirección General de Investigación (PPQ-2002-04414-C02-01

Analysis of solar direct irradiance models under clear-skies: Evaluation of the improvements for locally adapted models

Direct solar irradiance has to be determined for the design of many energy applications such as photovoltaic systems and concentration systems, and the generation of solar potential maps for energy use. Knowledge of the accurate values of radiation components in a local area will allow optimal sizing of solar energy conversion systems. The estimated values of direct solar irradiance from models are still necessary at those sites where no measurements are available. In this work, different models used for the estimation of the direct component of solar irradiance are analyzed. First, an evaluation of the performance of eight existing original models was performed from which three were selected. Second, the selected models were calibrated to adapt them to our studied geographical area, which is the important aspect of this work, and an assessment of performance improvements for locally adapted models is reported. Experimental data consisted of hourly horizontal global, direct, and diffuse solar irradiance values, provided by the National Meteorological Agency in Spain (AEMET) for Madrid. Long-term data series, corresponding to a total period of time of 32 years (1980–2011), have been used in this study. Only clear sky models were treated at present. The three selected models were adapted to the specific location of Madrid, and root mean square error (RMSE) and mean-biased error were determined. By comparing the performance in the direct horizontal irradiance estimation from existing original and the corresponding locally adapted models, it is found that the values of RMSE decreased from 9.9% to 5.7% for the Louche model, from 7.8% to 7.4% for the Robledo-Soler model, and finally from 8.8% to 6.7% for the European Solar Radiation Atlas model. Thus, significant improvements can be reached when parametric models are locally adapted. In our case, it is up to approximately 4% for the Louche model. It is expected that calibrated algorithms presented in this work will be applicable to regions of similar climatic characteristics.Spanish Government (grant ENE2011-27511) and the Department of Culture and Education of the Regional Government of Castilla y León, Spain (grant BU358A12-2