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Astrocytes are highly abundant in the mammalian brain, and their functions are of vital importance for all aspects of development, adaption, and aging of the central nervous system (CNS). Mounting evidence indicates the important contributions of astrocytes to a wide range of neuropathies. Still, our understanding of astrocyte development significantly lags behind that of other CNS cells. We here combine immunohistochemical approaches with genetic fate‐mapping, behavioural paradigms, single‐cell transcriptomics, and in vivo two‐photon imaging, to comprehensively assess the generation and the proliferation of astrocytes in the dentate gyrus (DG) across the life span of a mouse. Astrogenesis in the DG is initiated by radial glia‐like neural stem cells giving rise to locally dividing astrocytes that enlarge the astrocyte compartment in an outside‐in‐pattern. Also in the adult DG, the vast majority of astrogenesis is mediated through the proliferation of local astrocytes. Interestingly, locally dividing astrocytes were able to adapt their proliferation to environmental and behavioral stimuli revealing an unexpected plasticity. Our study establishes astrocytes as enduring plastic elements in DG circuits, implicating a vital contribution of astrocyte dynamics to hippocampal plasticity.

Summary Low-density cell culture of the postnatal cerebellum, combined with live imaging and single-cell tracking, allows the behavior of postnatal cerebellar neural stem cells (NSCs) and their progeny to be monitored. Cultured cerebellar NSCs maintain their neurogenic nature giving rise, in the same relative proportions that exist in vivo, to the neuronal progeny generated by the three postnatal cerebellar neurogenic niches. This protocol describes the identification of the nature of the progeny through both post-imaging immunocytochemistry and patch-clamp recordings. For complete details on the use and execution of this protocol, please refer to Paniagua-Herranz et al. (2020b)., Graphical abstract, Highlights • Protocol to culture postnatal mouse cerebellar neural stem cells (NSCs) in low density • The behavior of isolated postnatal cerebellar NSC can be monitored at single-cell level • Protocol for simultaneous monitoring of the three postnatal cerebellar neurogenic niches • Procedures of live imaging and single cell tracking for lineage tracing, Low-density cell culture of the postnatal cerebellum, combined with live imaging and single-cell tracking, allows the behavior of postnatal cerebellar neural stem cells (NSCs) and their progeny to be monitored. Cultured cerebellar NSCs maintain their neurogenic nature giving rise, in the same relative proportions that exist in vivo, to the neuronal progeny generated by the three postnatal cerebellar neurogenic niches. This protocol describes the identification of the nature of the progeny through both post-imaging immunocytochemistry and patch-clamp recordings.

The scientific community represents an insatiable network with important needs related to the searching of information. The ever-broadening amount of domain-scientific on-line information that can be found requires increasingly sophisticated frameworks to manage it. Nevertheless, these frameworks are usually focused on specific useful functionalities and work more like expert systems than general purpose approaches. In order to ease the research process to the scientific community, the Unified Knowledge Compiler (UNIKO) framework is presented. This framework includes, among other functionalities, the recommendation of articles and authors related to a specific field of application, the evaluation of reputation scores of articles and authors, and the sentiment analysis of the texts of the articles. UNIKO is built as a hybrid framework based on Knowledge-Based Systems and Content-Based Recommendation Systems. In order to evaluate the performance of the system, several experiments have been done. The first experiment is developed to illustrate the reputation scoring task. The second one addresses the sentiment scores calculation based on a lexicon which is supported by a Convolutional Neural Network. The last experiment shows the recommendation tasks based on specific similarity measures and unsupervised learning.

The objective of this research is to study the behaviour of the anaesthesia monitor Conox during natural sleep to open the gate for this devices to assess subjects during this stage. The values of qCON and qNOX indices and EEG frequency bands are analysed during night sleep of 10 volunteers when they lose consciousness, in order to determine if they can be used for monitoring sleep. The possibility of using these indexes to differentiate between NREM/REM cycles of night sleep is studied. A reduction in the hypnotic index was observed while the nociception index stayed significantly higher. Statistical differences where found for qCON between sleep cycles, allowing this index to detect REM intervals and possibly opening the gate to use depth of anaesthesia devices to monitor sleep.

The purinergic system is one of the oldest cell-to-cell communication mechanisms and exhibits relevant functions in the regulation of the central nervous system (CNS) development. Amongst the components of the purinergic system, the ionotropic P2X7 receptor (P2X7R) stands out as a potential regulator of brain pathology and physiology. Thus, P2X7R is known to regulate crucial aspects of neuronal cell biology, including axonal elongation, path-finding, synapse formation and neuroprotection. Moreover, P2X7R modulates neuroinflammation and is posed as a therapeutic target in inflammatory, oncogenic and degenerative disorders. However, the lack of reliable technical and pharmacological approaches to detect this receptor represents a major hurdle in its study. Here, we took advantage of the P2rx7-EGFP reporter mouse, which expresses enhanced green fluorescence protein (EGFP) immediately downstream of the P2rx7 proximal promoter, to conduct a detailed study of its distribution. We performed a comprehensive analysis of the pattern of P2X7R expression in the brain of E18.5 mouse embryos revealing interesting areas within the CNS. Particularly, strong labelling was found in the septum, as well as along the entire neural roof plate zone of the brain, except chorioidal roof areas, but including specialized circumventricular roof formations, such as the subfornical and subcommissural organs (SFO; SCO). Moreover, our results reveal what seems a novel circumventricular organ, named by us postarcuate organ (PArcO). Furthermore, this study sheds light on the ongoing debate regarding the specific presence of P2X7R in neurons and may be of interest for the elucidation of additional roles of P2X7R in the idiosyncratic histologic development of the CNS and related systemic functions., This work was supported by grants “Red de Excelencia Consolider-Ingenio Spanish Ion Channel Initiative” (BFU2015-70067REDC) from the Ministry of Economy and Competitiveness (BFU2014-53654-P), BRADE-Comunidad de Madrid (S2013/ICE-2958), UCM-Santander (PR26/16-18B-3; PR75/18) and Fundación Ramón Areces Grant program (PR2018/16–02). Maria Benito Leon is recipient of a contract from the “Fondo de Garantía Juvenil, Comunidad de Madrid” CAM PEJD-2016/BMD-2572. Felipe Ortega acknowledges support from the Ramon y Cajal Program of the Spanish Ministry of Economy and Competitiveness (MEC: RYC-2013–13290). This work has been also supported by Comunidad de Madrid, project “S2017/BMD-3867 (RENIM-CM)”, co-funded by European Structural and Investment Fund. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015–0505). MVG has been supported by Ministerio de Ciencia, Innovación y Universidades, ISCIII-FIS grants PI18/00462 co-financed by ERDF, European Union (FEDER) Funds from the European Commission, European Union, “A way of making Europe”.

Outlier trajectory detection systems have received growing attention over the last decades. These systems have highly improved their efficiency through the rise of the Internet of Things (IoT) and the emergence of affordable wireless sensor networks. IoT-based technologies adoption have led to a faster capture of data from several independent information sources with higher quality and greater volume. Besides, data mining and machine learning techniques allow the combination of these data sources in order to boost decision-making processes. In this paper, Outlier Detection in Animal Multivariate Trajectories (ODAMT) is proposed as a new method that combines spatial information with additional independent data sources for detection of anomalies in animal multivariate trajectories. ODAMT has been applied for the detection of cattle reproductive events in a real study achieving promising results.

Summary Little is known about the intrinsic specification of postnatal cerebellar neural stem cells (NSCs) and to what extent they depend on information from their local niche. Here, we have used an adapted cell preparation of isolated postnatal NSCs and live imaging to demonstrate that cerebellar progenitors maintain their neurogenic nature by displaying hallmarks of NSCs. Furthermore, by using this preparation, all the cell types produced postnatally in the cerebellum, in similar relative proportions to those observed in vivo, can be monitored. The fact that neurogenesis occurs in such organized manner in the absence of signals from the local environment, suggests that cerebellar lineage progression is to an important extent governed by cell-intrinsic or pre-programmed events. Finally, we took advantage of the absence of the niche to assay the influence of the vesicular nucleotide transporter inhibition, which dramatically reduced the number of NSCs in vitro by promoting their progression toward neurogenesis., Graphical Abstract, Highlights • We present a preparation that allows monitoring the behavior of cerebellar NSCs • Isolated NSCs maintain their neurogenic nature in absence of niche factors • The model enables monitoring the three postnatal cerebellar niches simultaneously • VNUT influences the balance between quiescence and activation of cerebellar NSCs, In this article, Ortega and colleagues describe a cell preparation that allows, in combination with live imaging, monitoring the behavior of NSCs from the three postnatal cerebellar niches. The authors provide evidence that, despite the absence of niche signals, isolated NSCs maintain their neurogenic nature and suggest a role for VNUT in the decision between quiescence and activation of cerebellar NSCs.

Aims: Left ventricular (LV) dyssynchrony lengthens the left ventricular electrical delay (LVED), measured from QRS onset to the first peak of the LV electrogram. We constructed an ECG model to predict LVED noninvasively. Methods: Intrapatient LVED was measured during a baseline vs nonselective His bundle pacing (nHBP) protocol. This setup provided paired synchronic/non-synchronic LVEDs, allowing intrapatient comparisons. Crosscorrelation of leads II and V 6 was accomplished and extracted features together with age and gender fed a linear mixed effects model to predict LVED. Results: Hemodynamic increments were consistent with LVED advances under nHBP in a subset of 17 patients (dP/dt max , baseline: 938.82 ± 241.95 mm Hg/s vs nHBP: 1034.94 ± 253.63 mm Hg/s, p = 6.24e-4). The inclusion of the area under V 6 (A V 6 ) and the time shift of R-peaks obtained from the crosscorrelation signal (Cor S ) grouped by patient significantly improved LVED estimation with respect to the model based only on QRS duration, age and gender (p = 1.7e-5). Conclusions: Interlead ECG changes explained LVED, providing clues about the electrical impulse conduction within the left ventricle noninvasively. Fil: Bonomini, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderón; Argentina. Universidad de Buenos Aires; Argentina Fil: Ortega, Daniel F.. Clínica San Camilo; Argentina. Hospital Universitario Austral; Argentina Fil: Barja, Luis D.. Clínica San Camilo; Argentina. Hospital Universitario Austral; Argentina Fil: Logarzo, Emilio. Clínica San Camilo; Argentina. Hospital Universitario Austral; Argentina Fil: Mangani, Nicolás. Clínica San Camilo; Argentina. Hospital Universitario Austral; Argentina Fil: Paolucci, Analía. Clínica San Camilo; Argentina. Hospital Universitario Austral; Argentina

Sentiment analysis is focused on detecting opinions and emotions directly linked to relevant topics in textual data. Its application for the automated analysis of large datasets with text from websites has become a major challenge today. Common approaches proposed for this task are based on predefined dictionaries of words, each one tagged with a positive or negative polarity beforehand. A known limitation of these systems is that they may return inaccurate estimations of the polarity of opinions, according to the actual number of words considered in the analysis. In addition, these systems do not usually include an intuitive graphical interface to facilitate the understanding of similarities between terms or gauge how their sentiment polarization evolves over time. In this paper we present EmoWeb, a prototype of a new tool for dynamic sentiment analysis of textual content from websites. This prototype includes a visual and dynamic framework to analyze texts, based on a well-established lexicon. An unsupervised learning algorithm can append new words and calculate or update their sentiment polarization and strength over time. Moreover, it can increase the number of words considered for sentiment analysis to improve the accuracy of results. A novel dynamic visualization module makes it easier for end users to interpret sentiments associated to terms and their changes. The prototype has been empirically evaluated in two experiments with real data gathered from news websites. Results are promising and illustrate the applicability of this approach for sentiment analysis of textual web content.

This text begins by defining a theoretical framework that serves as a basis for understanding what is Violence and what its forms are in the Colombian context; In addition to how these, have marked the national artistic expressions, mainly in the Cinema. This framework will be used to determine how we should approach the study of the phenomena of Violence in the reality, to later understand the reflexes of this in fiction.In the second part, a descriptive-critical sweep of the main Colombian films is made, which includes within its arguments components of Violence proper to the national reality; In this segment the manifestations of Violence are framed in two topics: Political Violence and Narco Violence.In conclusion, we will analyze the Colombian feature film "La sirga" by William Vega, 2012. Emphasizing how this production approaches Violence from the technical and conceptual aspect of the image, and the narrative work in the construction of the script, all with a view to Development of a "Post-Conflict" cinema.

Aims: His bundle pacing has shown to prevent detrimental effects from right ventricular apical pacing (RVA) and proved to resynchronize many conduction disturbances cases. However, the extent of His bundle pacing resynchronization is limited. An optimized stimulation waveform could expand this limit when implemented in His bundle pacing sets. In this work, we temporarily implemented RVA and Non-selective His bundle pacing with a biphasic anodal-first waveform (AF-nHB) and compared their effects against sinus rhythm (SR). Methods and results: Fifteen patients referred for electrophysiologic study with conduction disturbances, cardiomyopathy and ejection fraction below 35% were enrolled for the study. The following acute parameters were measured: QRS duration, left ventricular activation (RLVT), time of isovolumic contraction (IVCT), ejection fraction (EF), and dP/dtmax. QRS duration and RLVT decreased markedly under AF-nHB (SR: 169 ± 34 ms vs. nHB: 116 ± 31 ms, P

Live imaging and single cell tracking enables researchers to monitor crucial aspects of the biology of neural populations. In this commentary, we highlight the requirements, applications, and limitations of a protocol recently published by our research group. This protocol involves adapting the culture of several types of neural cells to time-lapse video microscopy, and the post-processing of the data to track distinct cell populations.

Calcium is one of the most important intracellular messengers, triggering a wide range of cellular responses. Changes in intracellular free calcium concentration can be measured using calcium sensitive fluorescent dyes, which are either EGTA- or BAPTA-based organic molecules that change their spectral properties in response to Ca

A comprehensive understanding of the mechanisms controlling the behavior of cell populations with regenerative potential is the first step to design effective therapeutic strategies for many diseases. However, a precise description of the biological events involved, such as proliferation, differentiation, cell fate decisions, migration, or viability, may be hampered by the classical use of experiments based on end-point analysis. By contrast, live imaging and single cell tracking provides researchers with an accurate readout of these features in cells throughout an experiment. Here, we describe a protocol to apply time-lapse video microscopy and post-processing of the data to study critical aspects of the biology and the lineage progression of multiple neural populations.

Ventricular depolarization dispersion refers mainly to heterogeneity in interlead QRS durations. Here, we propose the spatial variance (SVd) to describe depolarization dispersion about a mean QRS morphology. We hypothesize that waveform changes can be more accurate than interval changes at measuring QRS heterogeneity, and less sensitive to delineation errors. To prove this, SVd was computed on 36 dyssyn-chrony patients either in sinus rhythm (SVdB) or under nHB (SVdHB), and on 32 control subjects with native conduction (SVdN). In the normal ECG, there are interlead sets that produce maximal (SVdNmax) and minimal (SVdNmin) spatial variance. In Baseline patients, SVdB significantly increased from controls in the minimal variance situation (p < 0.005), deviating one or more leads from the normal morphology (similar in all the ensemble) and consequently increasing the interlead distance. The opposite held for the maximal variance situation, where it was expected a wide span of morphologies in health, there was a tendency to stacking in morphologies at baseline (p

The emergence of affordable wireless sensors has enabled the development of information systems combining sophisticated data processing and machine learning algorithms for pattern recognition. In many cases, these systems deal with time-series data, continuously gathered by sensors that compile detailed activity records. However, these datasets are frequently affected by numerous problems, including noisy data acquisition, missing data and utilization of inefficient techniques for information representation, which lead to deficient performance in machine learning applications. In this paper, we introduce a novel method to combine the efficient symbolic representation of time-series data with machine learning to improve the performance of classification systems tailored to detection of behavioural patterns of interest.

Voice transmission is no longer the main usage of mobile phones. Data transmissions, in particular Internet access, are very common actions that we might perform with these devices. However, the spectacular growth of the mobile data demand in 5G mobile communication systems leads to a reduction of the resources assigned to each device. Therefore, to avoid situations in which the Quality of Experience (QoE) would be negatively affected, an automated system for degradation detection of video streaming is proposed. This approach is named QoE Management for Mobile Users (QoEMU). QoEMU is composed of several modules to perform a real-time analysis of the network traffic, select a mitigation action according to the information of the traffic and to some predefined policies, and apply these actions. In order to perform such tasks, the best Key Performance Indicators (KPIs) for a given set of video traces are selected. A QoE Model is trained to define a global QoE for the set of traces. When an alert regarding degradation in the quality appears, a proper mitigation plan is activated to mitigate this situation. The performance of QoEMU has been evaluated over a degradation situation experiments with different video users.

Introducción: el objetivo fue identificar determinantes sociales de salud, en el ámbito familiar, en preescolares de Anapoima, Cundinamarca, y su relación con la prevalencia de experiencia de caries. Métodos: en el marco de la Alianza por un Futuro Libre de Caries-Capítulo Colombia (AFLC-CC), se valoró la prevalencia de experiencia de caries en niños preescolares de Anapoima, Cundinamarca, usando el Sistema Internacional de Detección y Valoración de Caries (ICDAS) y el índice ceod (cariados, extraídos y obturados, por diente), y se caracterizaron sus familias y viviendas. Se hizo análisis descriptivo y usando chi2 se exploraron asociaciones entre ceod e ICDAS y condiciones socioeconómicas, de infraestructura y prácticas de salud en las familias. Resultados: se valoraron 120 niños de jardines infantiles del municipio de Anapoima y se visitaron sus hogares. La prevalencia de experiencia de caries (ceod) fue de 33,3% (promedio: 1,3 ± 2,5); al incluir lesiones iniciales, fue de 46,7% (4,3 ± 7,0). Se encontró relación entre presencia de caries y tipo de problemas de salud bucal referidos por los padres, relación filial con el cuidador, asistencia al servicio de salud bucal y disponibilidad de un espacio para el cepillo (p < 0,05). Conclusiones: los niños valorados presentaron baja experiencia de caries, en comparación con referentes nacionales, lo cual se explica por los determinantes intermedios identificados en su ámbito familiar, en los que se evidencian condiciones económicas, de infraestructura y de conformación familiar favorables para las prácticas de salud. Es necesario profundizar en la comprensión de la relación entre determinantes sociales y salud bucal desde la esfera estructural y fortalecer las estrategias en salud, con miras a lograr poblaciones libres de caries.

For the past three decades, our laboratory has conducted pioneering research to elucidate the complexity of purinergic signaling in the CNS, alone and in collaboration with other groups, inspired by the ground-breaking efforts of Geoffrey Burnstock. This review summarizes our contribution to understand the nucleotide receptor signaling in the CNS with a special focus on the P2X7 receptor.

Brain injury generates the release of a multitude of factors including extracellular nucleotides, which exhibit bi-functional properties and contribute to both detrimental actions in the acute phase and also protective and reparative actions in the later recovery phase to allow neuroregeneration. A promising strategy toward restoration of neuronal function is based on activation of endogenous adult neural stem/progenitor cells. The implication of purinergic signaling in stem cell biology, including regulation of proliferation, differentiation, and cell death has become evident in the last decade. In this regard, current strategies of acute transplantation of ependymal stem/progenitor cells after spinal cord injury restore altered expression of P2X4 and P2X7 receptors and improve functional locomotor recovery. The expression of both receptors is transcriptionally regulated by Sp1 factor, which plays a key role in the startup of the transcription machinery to induce regeneration-associated genes expression. Finally, general signaling pathways triggered by nucleotide receptors in neuronal populations converge on several intracellular kinases, such as PI3K/Akt, GSK3 and ERK1,2, as well as the Nrf-2/heme oxigenase-1 axis, which specifically link them to neuroprotection. In this regard, regulation of dual specificity protein phosphatases can become novel mechanism of actions for nucleotide receptors that associate them to cell homeostasis regulation.This article is part of the Special Issue entitled ‘Purines in Neurodegeneration and Neuroregeneration’.

Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thus, our work uncovers a novel function of Prox1 as a fate determinant for oligodendrocytes in the adult mammalian brain. These data indicate that the neurogenic and oligodendrogliogenic lineages in the two adult neurogenic niches exhibit a distinct requirement for Prox1, being important for neurogenesis in the DG but being indispensable for oligodendrogliogenesis in the SVZ.

Despite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independentrole, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-wide expression analysis confirmed that treatments promoting neuronal reprogramming elicit an anti-oxidative stress response. Importantly, co-expression of Bcl-2 and anti-oxidative treatments leads to an unprecedented improvement in glial-to-neuron conversion after traumatic brain injury invivo, underscoring the relevance of these pathways in cellular reprograming irrespective of cell type invitro and invivo.

Nucleotides can contribute to the survival of different glial and neuronal models at the nervous system via activation of purinergic P2X and P2Y receptors. Their activation counteracts different proapoptotic events, such as excitotoxicity, mitochondrial impairment, oxidative stress and DNA damage, which concur to elicit cell loss in different processes of neurodegeneration and brain injury. Thus, it is frequent to find that different neuroprotective mediators converge in the activation of the same intracellular survival pathways to protect cells from death. The present review focuses on the role of P2Y1 and P2Y13 metabotropic receptors, and P2X7 ionotropic receptors to regulate the balance between survival and apoptosis. In particular, we analyze the intracellular pathways involved in the signaling of these nucleotide receptors to elicit survival, including calcium/PLC, PI3K/Akt/GSK3, MAPK cascades, and the expression of antioxidant and antiapoptotic genes. This review emphasizes the novel contribution of nucleotide receptors to maintain cell homeostasis through the regulation of MAP kinases and phosphatases. Unraveling the different roles found for nucleotide receptors in different models and cellular contexts may be crucial to delineate future therapeutic applications based on targeting nucleotide receptors for neuroprotection.

Uno de los principales problemas de salud en menores de 6 años son las parasitosis intestinales,estas surgen por falta de higiene, así como por el subdesarrollo en zonas tanto urbanas comorurales de México. En este estudio se determinó la prevalencia de parasitosis y desnutrición eninfantes de la comunidad indígena de Bacame Nuevo, Sonora, por medio un estudio descriptivoen donde participó una población de 71 niños de 4 a 6 años a los cuales al 26.8% se les realizaronanálisis de heces mediante los métodos (directo en fresco y con lugol), método de Faust, elmétodo de sedimentación con Brij L23, 30%. Al 100% de la población de estudio se lesdeterminó su estado de nutrición mediante evaluaciones antropométricas (EA) utilizando lasnormas de crecimiento establecidas por la OMS y CDC. Encontramos que 94.7% de los niñosanalizados presentó multiparasitosis hasta con 6 organismos diferentes. Este valor coincide conel reporte del SINAVE a nivel nacional, para infecciones por protozoarios y helmintos conmayor incidencia en este rango de edad. En la evaluación nutricional 35% de los niñospresentaron valores bajos de grasa corporal, 2% de delgadez extrema, 21.12 % macrocefaleacon respecto a su peso y edad, lo cual es un signo claro de desnutricion crónica y 48% de losniños analizados presentaron perímetros de cintura aumentados para su edad y talla, lo cual masque ser un indicativo de riesgo cardiovascular (ICC) es un reflejo de inflamación abdominalcaracterística de las parasitosis.

In the age of communication, piracy and copyright violations are emerging as a primary problem in our society. These issues produce an increasing loss of money and non-desirable situations in business. In order to provide some support, governments have approved multiple laws projects to toughen the legality. However, more efforts must be made in order to detect this illegal content and enforce the law. For this purpose, it is desirable to develop automatic tools which achieve this job. In this paper it is presented a framework based on a binary classifier which has been trained through supervised learning techniques. This classifier is able to label a website (as legal or not) focusing only on the URL domain. The work aim is experimental, hence we have used text processing techniques, several similarity metrics and different classification models, in order to evaluate the resulting outcomes. These latter have been promising, given a firm line of work in future.

Understanding the mechanisms that control critical biological events of neural cell populations, such as proliferation, differentiation, or cell fate decisions, will be crucial to design therapeutic strategies for many diseases affecting the nervous system. Current methods to track cell populations rely on their final outcomes in still images and they generally fail to provide sufficient temporal resolution to identify behavioral features in single cells. Moreover, variations in cell death, behavioral heterogeneity within a cell population, dilution, spreading, or the low efficiency of the markers used to analyze cells are all important handicaps that will lead to incomplete or incorrect read-outs of the results. Conversely, performing live imaging and single cell tracking under appropriate conditions represents a powerful tool to monitor each of these events. Here, a time-lapse video-microscopy protocol, followed by post-processing, is described to track neural populations with single cell resolution, employing specific software. The methods described enable researchers to address essential questions regarding the cell biology and lineage progression of distinct neural populations., Journal of Visualized Experiments. JoVE, 2017 (130), ISSN:1940-087X

The epithelial to mesenchymal transition (EMT) is a biological process in which cells lose cell-cell contacts and become motile. EMT is used during development, for example, in triggering neural crest migration, and in cancer metastasis. Despite progress, the dynamics of JNK signaling, its role in genomewide transcriptional reprogramming, and involved downstream effectors during EMT remain largely unknown. Here, we show that JNK is not required for initiation, but progression of phenotypic changes associated with EMT. Such dependency resulted from JNK-driven transcriptional reprogramming of critical EMT genes and involved changes in their chromatin state. Furthermore, we identified eight novel JNK-induced transcription factors that were required for proper EMT. Three of these factors were also highly expressed in invasive cancer cells where they function in gene regulation to maintain mesenchymal identity. These factors were also induced during neuronal development and function in neuronal migration in vivo. These comprehensive findings uncovered a kinetically distinct role for the JNK pathway in defining the transcriptome that underlies mesenchymal identity and revealed novel transcription factors that mediate these responses during development and disease.

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) play a central role in the intracellular signaling of P2X7 nucleotide receptors in neurons and glial cells. Fine spatio-temporal tuning of mitogen-activated protein (MAP) kinases is essential to regulate their biological activity. MAP kinase phosphatases (MKPs) are dual specificity protein phosphatases (DUSPs) that dephosphorylate phosphothreonine and phosphotyrosine residues in MAP kinases. This study focuses on how DUSP, DUSP6/MKP3, a phosphatase specific for ERK1/2 is regulated by the P2X7 nucleotide receptor in cerebellar granule neurons and astrocytes. Stimulation with the specific P2X7 agonist, BzATP, or epidermal growth factor (EGF) (positive control for ERK activation) regulates the levels of DUSP6 in a time dependent manner. Both agonists promote a decline in DUSP6 protein, reaching minimal levels after 30 min yet recovering to basal levels after 1 h. The initial loss of protein occurs through proteasomal degradation, as confirmed in experiments with the proteasome inhibitor, MG-132. Studies carried out with Actinomycin D demonstrated that the enhanced transcription of the Dusp6 gene is responsible for recovering the DUSP6 protein levels. Interestingly, ERK1/2 proteins are involved in the biphasic regulation of the protein phosphatase, being required for both the degradation and the recovery phase. We show that direct Ser197 phosphorylation of DUSP6 by ERK1/2 proteins could be part of the mechanism regulating their cytosolic levels, at least in glial cells. Thus, the ERK1/2 activated by P2X7 receptors exerts positive feedback on these kinase’s own activity, promoting the degradation of one of their major inactivators in the cytosolic compartment, DUSP6, both in granule neurons and astrocytes. This feedback loop seems to function as a common universal mechanism to regulate ERK signaling in neural and non-neural cells.

The distribution of nucleotide P2Y receptors across different tissues suggests that they fulfil key roles in a number of physiological and pathological conditions. P2Y

While the adult subependymal zone (SEZ) harbors pools of distinct neural stem cells that generate different types of GABAergic interneurons, a small progenitor population in the dorsal SEZ expresses Neurog2 and gives rise to glutamatergic neurons. Here we investigated whether SEZ progenitors can be programmed towards glutamatergic neurogenesis through forced expression of Neurog2. Retrovirus-mediated expression of Neurog2 induced the glutamatergic neuron lineage markers Tbr2 and Tbr1 in cultured SEZ progenitors which subsequently differentiated into functional glutamatergic neurons. Likewise, retrovirus-mediated expression of Neurog2 in dividing SEZ progenitors within the adult SEZ induced Tbr2 and Tbr1 expression, hallmarking entry into the glutamatergic lineage also in vivo. Intriguingly, Neurog2-expressing progenitors failed to enter the rostral migratory stream (RMS) and instead differentiated directly within the SEZ or the adjacent striatum. In sharp contrast, lentivirus-mediated postmitotic expression of Neurog2 failed to reprogram early SEZ neurons, which instead maintained their GABAergic identity and migrated along the RMS towards the olfactory bulb. Thus, our data show that Neurog2 can program SEZ progenitors towards a glutamatergic identity, but fails to reprogram their postmitotic progeny.Summary statementOur study identifies a critical developmental time window during which progenitors of the adult subependymal zone, specified for generating GABAergic neurons, can be reprogrammed towards glutamatergic neurogenesis.

El valor de la fiesta en México es casi religioso. Está ligado a la renovación del espacio y del tiempo. Cada fiesta implica a la vez interrupción de una secuencia lineal, conmemoración, comunión o encuentro físico con los otros. Una oportunidad para volver al origen, al estadio primordial en el que cada uno se funde con el todo, la gran mezcla universal, el baño en las aguas del comienzo. Esto explica que las fiestas cívicas, las religiosas y las manifestaciones multitudinarias no sean la excepción, sino la regla que confirma esa necesidad del ser social del mexicano a lo largo de los siglos. Aquí, por ser un país milenario de enorme diversidad cultural, los festejos para celebrar a la nación adoptarían una significación polisémica en ese mismo sentido: sus componentes cósmico-rituales simbolizarían a la vez un retorno a la tierra, un reclamo a despertar la semilla y un zambullido a los antiguos símbolos; una concelebración anónima capaz de conjugar simultáneamente el ejercicio del poder teocrático, el amor y respeto a los ancestros, la condición inescapable de estar juntos, y el cumplimiento de plazos calendáricos específicos. The value of celebrations in Mexico is almost religious. It is linked to renewal of space and time. Each feast involves both the interruption of a linear sequence, commemoration, communion or physical encounter with others. An opportunity to return to the source, the primordial stage in which each one merges with the whole, the great universal mix, bathing in the waters of the beginning. This explains why civic and religious festivals, and also mass demonstrations are not the exception, but a social Mexican necessity which confirms the rule throughout centuries. Being a millenary country of enormous cultural diversity, festivities to celebrate Mexico as independent nation would adopt a polysemic significance along the same lines: their cosmic and ritual components symbolize both a return to the land, a claim to awaken the seed and an immersion at the ancient symbols. Meaning, an anonymous remembrance able to combine simultaneously the exercise of theocratic power, love and respect for the ancestors, the inescapable condition of being together, and the compliance with specific calendrical deadlines.

Combinations of neuronal determinants and/or small-molecules such as Forskolin (Fk) can be used to convert different cell types into neurons. As Fk is known to activate cAMP-dependent pathways including CREB-activity, we aimed here to determine the role of CREB in reprogramming – including its temporal profile. We show that transient expression of the dominant-positive CREB-VP16 followed by its inactivation mediated by the dominant-negative ICER improves neuronal conversion of astrocytes mediated by the neurogenic determinant Ascl1. Contrarily, persistent over-activation by CREB-VP16 or persistent inhibition by ICER interferes with neuronal reprogramming, with the latter enhancing cell death. Taken together our work shows transient CREB activation as a key effector in neuronal reprogramming.

Adult neural stem cells reside in a specialized niche in the subventricular zone (SVZ). Throughout life they give rise to adult-born neurons in the olfactory bulb (OB), thus contributing to neural plasticity and pattern discrimination. Here, we show that the neurovascular protein EGFL7 is secreted by endothelial cells and neural stem cells (NSCs) of the SVZ to shape the vascular stem-cell niche. Loss of EGFL7 causes an accumulation of activated NSCs, which display enhanced activity and re-entry into the cell cycle. EGFL7 pushes activated NSCs towards quiescence and neuronal progeny towards differentiation. This is achieved by promoting Dll4-induced Notch signalling at the blood vessel-stem cell interface. Fewer inhibitory neurons form in the OB of EGFL7-knockout mice, which increases the absolute signal conducted from the mitral cell layer of the OB but decreases neuronal network synchronicity. Consequently, EGFL7-knockout mice display severe physiological defects in olfactory behaviour and perception., The vascular stem cell niche regulates the proliferation and differentiation of neural stem cells (NSCs) in the adult subventricular zone. Here the authors identify EGFL7 as a neurovascular regulator of NSCs in vivo; EGFL7-knockout mice show reduced neurogenesis, and exhibit impaired olfactory perception and behaviour.

The distribution of nucleotide P2Y receptors across different tissues suggests that they fulfil key roles in a number of physiological and pathological conditions. P2Y13 is one of the latest P2Y receptors identified, a novel member of the Gi-coupled P2Y receptor subfamily that responds to ADP, together with P2Y12 and P2Y14. Pharmacological studies drew attention to this new ADP receptor, with a pharmacology that overlaps that of P2Y12 receptors but with unique features and roles. The P2RY12–14 genes all reside on human chromosome 3 at 3q25.1 and their strong sequence homology supports their evolutionary origin through gene duplication. Polymorphisms of P2Y13 receptors have been reported in different human populations, yet their consequences remain unknown. The P2Y13 receptor is versatile in its signalling, extending beyond the canonical signalling of a Gi-coupled receptor. Not only can it couple to different G proteins (Gs/Gq) but the P2Y13 receptor can also trigger several intracellular pathways related to the activation of MAPKs (mitogen-activated protein kinases) and the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 axis. Moreover, the availability of P2Y13 receptor knockout mice has highlighted the specific functions in which it is involved, mainly in the regulation of cholesterol and glucose metabolism, bone homeostasis and aspects of central nervous system function like pain transmission and neuroprotection. This review summarizes our current understanding of this elusive receptor, not only at the pharmacological and molecular level but also, in terms of its signalling properties and specific functions, helping to clarify the involvement of P2Y13 receptors in pathological situations.

La parasitosis intestinal constituye un problema de salud pública en México, siendo la población infantil la más afectada (9). En el estado de Sonora, se han realizado estudios que ubican la prevalencia de infecciones por microorganismos como Giardia lamblia, Endolimax nana y Entamoeba coli en 20, 10 y 19% respectivamente, con una situación de poliparasitismo en 18% de los casos (6). El hacinamiento, la escasez del agua potable y la carencia de drenaje, constituyen los mayores factores de riesgo para contraer este tipo de enfermedad (1). Como parte de un proyecto de Servicio Social de la Carrera de Químico Biólogo de la Universidad de Sonora, Unidad Regional Sur, se realizó un muestreo coproparasitoscópico en 52 niños de entre Primer y Cuarto grado de educación Primaria, en una población ejidal del sur del estado, con el fin de detectar casos positivos y canalizarlos para su atención. Se registraron 40 casos positivos para parasitosis, representando un 76.9% de la muestra, los principales microorganismos detectados durante el estudio fueron G. lamblia, E. histolityca, E. coli y E. nana, encontrándolos de manera aislada o en algunas muestras en asociaciones multiparasitarias.