Senescence induction; a possible cancer therapy

Cellular immortalization is a crucial step during the development of human cancer. Primary mammalian cells reach replicative exhaustion after several passages in vitro, a process called replicative senescence. During such a state of permanent growth arrest, senescent cells are refractory to physiological proliferation stimuli: they have altered cell morphology and gene expression patterns, although they remain viable with preserved metabolic activity. Interestingly, senescent cells have also been detected in vivo in human tumors, particularly in benign lesions. Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. During immortalization, cells acquire genetic alterations that override senescence. Tumor suppressor genes and oncogenes are closely involved in senescence, as their knockdown and ectopic expression confer immortality and senescence induction, respectively. By using high throughput genetic screening to search for genes involved in senescence, several candidate oncogenes and putative tumor suppressor genes have been recently isolated, including subtypes of micro-RNAs. These findings offer new perspectives in the modulation of senescence and open new approaches for cancer therapy

ABP y Scrum como herramientas para la participación en el programa FLL

FIRST Lego League es una competición internacional organizada por FIRST (For Inspiration and Recognition of Science and Technology, organización sin ánimo de lucro) para estudiantes de primaria y secundaria, que implica los productos y tecnologías desarrollados por Lego. Cada año se presenta un desafío científico del mundo real diferente. El programa se compone de dos partes principales. Por un lado, el diseño y programación de un robot, con el objetivo de que complete el máximo número de misiones planteadas en un tiempo limitado. Y por otro, cada grupo debe presentar una propuesta tecnológica innovadora relacionada con la temática anual de la competición. La presentación se acompaña de una maqueta y cartel descriptivos. Este año la temática es la ciudad y el entorno en el que vivimos (temáticas de otros años: los residuos, el agua, el espacio,...). Este documento presenta una propuesta para la participación en este programa dentro la asignatura de Tecnología de 4º de ESO (aunque sería interesante ampliar el proyecto a otros cursos, e incluso asignaturas). El juego del robot se desarrollará dentro de un marco de desarrollo tipo Scrum. Y para el proyecto de innovación se aplicará una metodología basada en proyectos (ABP). Que consistirá en un trabajo en equipo orientado a solucionar algún problema o plantear alguna mejora en las instalaciones de nuestras viviendas (agua, gas, electricidad,...) u otros edificios de nuestra ciudad.<br /

An integrated biogeochemistry observation system at Besòs estuary

Estuaries are coastal indentations where freshwater mixes with seawater (Pritchard 1967), and are found everywhere in the world. Moreover, the estuarine ecosystems are usually characterized by high biological productivity and great biodiversity. However, these characteristics are very sensitive to the climate regime, the geological environment and the hydrological quality. In metropolitan environments with high social, urban and economic complexity, river fows usually play an important role in the regulation of estuary biochemistry, and therefore their control is essential. Such estuary, is the one generated by the Besós river, located in the north of Barcelona, where the management of the water cycle of its riverbed and its mouth is a shared strategy for the development of the territory between the municipality of Sant Adriá del Besòs, the town hall of Badalona, the Consorci del Besòs, the Polytechnic University of Catalonia and the b_TEC Foundation. These institutions share the Territorial Specialization and Territorial Competitiveness Project (PECT) of the Besòs Sustainable Territory coast, where one of its objectives is the improvement and use of water and coastal resources in the Besòs environment. In this framework, it is intended to reduce the impact of heavy rain scenarios and frequent sewer overfows, which involve poor water quality scenarios on the beaches near the river mouth, through the use of surplus groundwater to improve the water quality of the riverbed, instead of being sent to the sewer. To evaluate the degree of improvement provided by this solution, in the Besòs estuary it has been deployed and installed a new integrated biogeochemistry observatory that includes (a) a costal buoy with a multi-sensor system and (b) a riverbed platform with a multi-sensor system as shown in Figure 1, that provide long series of real-time data.Peer Reviewe

Retinal Organoids derived from hiPSCs of an AIPL1-LCA Patient Maintain Cytoarchitecture despite Reduced levels of Mutant AIPL1

Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is a photoreceptor-specific chaperone that stabilizes the effector enzyme of phototransduction, cGMP phosphodiesterase 6 (PDE6). Mutations in the AIPL1 gene cause a severe inherited retinal dystrophy, Leber congenital amaurosis type 4 (LCA4), that manifests as the loss of vision during the first year of life. In this study, we generated three-dimensional (3D) retinal organoids (ROs) from human induced pluripotent stem cells (hiPSCs) derived from an LCA4 patient carrying a Cys89Arg mutation in AIPL1. This study aimed to (i) explore whether the patient hiPSC-derived ROs recapitulate LCA4 disease phenotype, and (ii) generate a clinically relevant resource to investigate the molecular mechanism of disease and safely test novel therapies for LCA4 in vitro. We demonstrate reduced levels of the mutant AIPL1 and PDE6 proteins in patient organoids, corroborating the findings in animal models; however, patient-derived organoids maintained retinal cell cytoarchitecture despite significantly reduced levels of AIPL1.This work was supported by Institute of Health Carlos III (ISCIII)/ ERDF (European Research Development Fund), Spain, ((PI16/00409 (DL); DL, AAC, and SE are members of PRB3 supported by a grant (PT17/0019/0024) of the PE I + D + i 2013–2016, funded by ISCIII and ERDF. The work was also supported by ISCIII-ERDF (PI16/00425), CIBERER 06/07/0036, IIS-FJD Biobank PT13/0010/0012, RAREGENOMICS funded by Regional Government of Madrid, (CAM, B2017/BMD3721) and ERDF, the University Chair UAM-IIS-FJD of Genomic Medicine, the Spanish National Organization of the Blind (ONCE), the Spanish Fighting Blindness Foundation (FUNDALUCE), and the Ramon Areces Foundation. MC is supported by the Miguel Servet Program (CPII17_00006) from ISCIII. DL is supported by Miguel Servet I Program (CP18/00033). VR is supported by National Institute of Health (R01 EY028035, R01 EY025536). Transcriptome profiling and analyses were supported by the Intramural Research Program of the National Eye Institute (ZIAEY000450, ZIAEY000474) and utilized the high-performance computational capabilities of the Biowulf Linux cluster at NIH (http://biowulf.nih.gov)

Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3

The inhibition of glycogen synthase kinase-3 (GSK-3) can induce neurogenesis, and the associated activation of Wnt/β-catenin signaling via GSK-3 inhibition may represent a means to promote motor function recovery following spinal cord injury (SCI) via increased astrocyte migration, reduced astrocyte apoptosis, and enhanced axonal growth. Herein, we assessed the effects of GSK-3 inhibition in vitro on the neurogenesis of ependymal stem/progenitor cells (epSPCs) resident in the mouse spinal cord and of human embryonic stem cell-derived neural progenitors (hESC-NPs) and human-induced pluripotent stem cell-derived neural progenitors (hiPSC-NPs) and in vivo on spinal cord tissue regeneration and motor activity after SCI. We report that the treatment of epSPCs and human pluripotent stem cell-derived neural progenitors (hPSC-NPs) with the GSK-3 inhibitor Ro3303544 activates β-catenin signaling and increases the expression of the bIII-tubulin neuronal marker; furthermore, the differentiation of Ro3303544-treated cells prompted an increase in the number of terminally differentiated neurons. Administration of a water-soluble, bioavailable form of this GSK-3 inhibitor (Ro3303544-Cl) in a severe SCI mouse model revealed the increased expression of bIII-tubulin in the injury epicenter. Treatment with Ro3303544-Cl increased survival of mature neuron types from the propriospinal tract (vGlut1, Parv) and raphe tract (5-HT), protein kinase C gamma-positive neurons, and GABAergic interneurons (GAD65/67) above the injury epicenter. Moreover, we observed higher numbers of newly born BrdU/DCX-positive neurons in Ro3303544-Cl-treated animal tissues, a reduced area delimited by astrocyte scar borders, and improved motor function. Based on this study, we believe that treating animals with epSPCs or hPSC-NPs in combination with Ro3303544-Cl deserves further investigation towards the development of a possible therapeutic strategy for SCI

miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-α, CCNJ, and MEGF9

MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3'-UTRs of ENPEP, CK2-alpha, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-alpha, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40-56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-alpha was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-alpha, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-alpha, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer

Validity and reliability of the international fItness scale (IFIS) in preschool children

Objectives Examine the validity and reliability of parent-reported International FItness Scale (IFIS) in preschoolers. Method A cross-sectional study of 3051 Spanish preschoolers (3-5 years). Fitness was measured by PREFIT battery and reported by parents using an adapted version of the IFIS. Waist circumference was evaluated, and the waist-to-height ratio (WHtR) was calculated. Seventy-six parents of randomly selected schoolchildren completed the IFIS twice for a reliability assessment. Results ANCOVA, adjusted for sex, age and WHtR, showed that preschoolers who were scored by their parents as having average-to-very good fitness had better levels of measured physical fitness than those preschoolers who were classified as having very poor/poor fitness levels (18.1laps to 22.1laps vs 15.6laps for cardiorespiratory fitness; 6.6 kg to 7.5 kg vs 5.3 kg for muscular fitness-handgrip-; 71.7 cm to 76.4 cm vs 62.0 cm for muscular fitness-standing long jump-; 17.2s to 16.2s vs 18.2s for speed/agility; and 11.2s to 15.6s vs 8.7s for balance; p < 0.001). The weighted kappa for concordance between parent-reported fitness levels and objective assessment was poor (kappa <= 0.18 for all fitness measures). Overall, the mean values of the abdominal adiposity indicators were significantly lower in high-level fitness categories reported by parents than in low-level fitness categories (p < 0.05). The test-retest reliability ranged from 0.46 to 0.62. Conclusions The reliability of the parent-reported IFIS are acceptable, but the concordance between parents reported and objectively measures fitness levels is poor, suggesting that parents' responses may not be able to correctly classify preschoolers according to their fitness level.The PREFIT project takes place thanks to the funding linked to the Ramon y Cajal grant held by Ortega FB (RYC-2011-09011)

IDENTIFICAÇÃO E RASTREAMENTO DE VEÍCULOS UTILIZANDO FLUXO ÓPTICO

Controlar o tráfego de veículos é uma tarefa muito difícil de ser realizada. Essa atividade representa um grande desafio na busca por soluções que possam ajudar o controle e a fiscalização de tráfego de veículos em vias terrestres. Neste trabalho considera-se o emprego do método diferencial, proposto por Lucas e Kanade, para estimação do Fluxo Óptico, como ferramenta computacional para rastrear e classificar veículos a partir de frames de imagens de vídeo. Os veículos encontrados em cada frame são classificados conforme o seu tamanho: pequeno, médio e grande porte. Os resultados deste trabalho podem ser aplicados, por exemplo, em sistemas de contagem de veículos em rodovias. Outra aplicação desse trabalho, que é de grande valia seria para a construção de semáforos inteligentes, que controlam os tempos de bloqueio e liberação da via baseados no fluxo de veículos

Human iPSC derived disease model of MERTK-associated retinitis pigmentosa

Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches.This work was supported by Andalusian Health Council (PI-0324-2013), Instituto de Salud Carlos III (PI13/01331), Spanish Ministry of Economy and Competitiveness-FEDER BFU2012-36845, Instituto de Salud Carlos III RETICS RD12/0034/0010 and Academy of Finland (218050; 272808)

The Efficacy of Short-Term Supplemental Nutrition Education on Nutrition Knowledge and Dietary Behaviors of Urban Middle School Children

Background: Children and adolescents are not meeting the dietary guidelines and overweight and obesity related diseases are on the rise among youth in the United States. However, research is inconsistent with regard to the most effective method of educating urban youth. Purpose: To determine the effect of a supplemental nutrition education on the knowledge and behaviors of urban school students. Methods: Six nutrition lessons were provided to students attending the Boys and Girls Club of Metro Atlanta (BGCMA) in Atlanta, GA. A pre- and posttest was administered to assess differences in students’ nutrition knowledge and behaviors. Chi-square analysis compared the number of correct answers for the entire intervention population and after stratification by gender and number of classes missed. The Wilcoxon signed rank test compared the median number of correct answers in pre- vs. posttest responses for all participants and by the number of classes missed. Results: 15 students enrolled in the study. 2 students did not complete the study. A significant but negative change in knowledge was found in 1 of 15 nutrition questions. A significant negative change in the median number of total answers correct on the pre- vs. posttest was also observed (p=0.049). Approximately 60% of the participants reported that they were more likely to make positive, nutrition-related behavior changes after the intervention. Conclusion: We found a negative association between the nutrition education intervention and knowledge gain. This study suggests that nutrition education alone does not have a significant effect on nutrition knowledge of urban youth