Paleogeografía sísmica de zonas costeras en la Península Ibérica: su impacto en el análisis de terremotos antiguos e históricos en España

This paper presents three examples of ancient earthquakes occurring in coastal areas of the S and SE of the Iberian Peninsula (218 BC, AD 40-60 and AD 1048) with the aim of illustrating the use of geological and archaeological data in their macroseismic characterization. Historical information for ancient earthquakes that occurred in Spain prior to the 10th century is scarce or non-existent. This paper shows that the current state of knowledge on palaeoseismology and archaeoseismology on these ancient events clearly exceeds the existing historical information allowing the increase of macroseismic information points by using the ESI-07 scale (Environmental Seismic Intensity). Consequently, the geologic analyses of ancient earthquakes contribute to their understanding and parametric evaluations, and improve further advances in seismic hazard assessments. The most significant issue outlined in the present paper is the analysis of the ancient palaeogeography of the affected areas. The studied examples analysed were located in open estuarine areas that have been filled by fluvial sediments or anthropogenic fills over time. The effects of the 218 BC earthquake-tsunami event in the Gulf of Cadiz are analysed in estuarine areas, and especially in the ancient Roman Lagus Ligustinus (Guadalquivir Depression marshes); the effects of the earthquake in AD 40-60 is analysed in the old Roman city of Baelo Claudia located in the Bolonia Bay (Strait of Gibraltar); and the effects of the earthquake of AD 1048on the ancient Sinus Ilicitanus (Bajo Segura Depression) during Muslim times. Descriptions from Roman and Arabic geographers are cross-checked with existing palaeogeographic models based on geological data. This type of analysis results in ancient macroseismic scenarios for the interpretation of theoretical distributions of intensities and environmental effects supporting the concept of “seismic palaeogeography” proposed in this paperEl presente trabajo recoge tres ejemplos de terremotos antiguos (218 AC, 40-60 AD y 1048 AD) ocurridos en zonas litorales del S y SO de la Península Ibérica con la intención de ilustrar el uso de datos geológicos y ar¬queológicos en la caracterización macrosísmica de los mismos. En la mayor parte de los sísmos ocurridos con anterioridad al siglo X d.C. la información documental histórica que se posee es muy escasa o inexistente. El presente trabajo muestra que el actual estado de conocimiento en paleosismología y arqueosismologia sobre este tipo de terremotos sobrepasa con creces la información documental histórica, permitiendo la multiplica¬ción de los puntos de información macrosísmica mediante el uso de la escala ESI-07 (Environmental Seismic Intensity). Consecuentemente, el análisis geológico de los terremotos antiguos mejora su conocimiento y análisis paramétrico, permitiendo avanzar la evaluación de la peligrosidad sísmica de las zonas afectadas. El aspecto que se pone de especial relieve en este trabajo es el análisis de la paleogeografía existente en la antigüedad, ya que todas las zonas (afectadas) analizadas en este trabajo corresponden a zonas estuarinas abiertas que se han ido rellenado por aportes fluviales o de forma artificial con el tiempo. Se analizan los efectos del terremoto de 218 AC en las zonas estuarinas del Golfo de Cádiz y muy especialmente en el antiguo Lacus Ligustinus (marismas del Guadalquivir) durante época romana; los efectos del terremoto de 40-60 AD en la antigua Bahía de Baelo Claudia (Estrecho de Gibraltar); y los efectos del terremoto de 1048 AD en el antiguo Sinus ilicitanus (Depresión del Bajo Segura) durante época musulmana. Se han cotejado descripciones de geógrafos romanos y árabes con modelos basados en datos geológicos. Este tipo de análisis ha permitido generar antiguos escenarios macrosísmicos basados en la paleogeografía y reinterpretar las distribuciones teóricas de intensidades y los efectos ambientales de los terremotos estudiados que es a lo que se refiere el concepto de “paleogeografía sísmica” propuesto en este trabajoThis work has been funded by the Spanish-FEDER research projects CGL2012-37281 C02.01 (QTECTBETICA-USAL), CGL2012-33430 (CSIC) and CGL2013-42847-R (UNED

New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well-defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified. Based on the hypothesis that BCR activation may depend on somatic mutations of the BCR and related pathways we have performed a complete mutational screening of 301 selected genes associated with BCR signaling and related pathways using massive parallel sequencing technology in 10 CLL cases. Four mutated genes in coding regions (KRAS, SMARCA2, NFKBIE and PRKD3) have been confirmed by capillary sequencing. In conclusion, this study identifies new genes mutated in CLL, all of them in cases with progressive disease, and demonstrates that next-generation sequencing technologies applied to selected genes or pathways of interest are powerful tools for identifying novel mutational changes

Artificial intelligence within the interplay between natural and artificial computation:Advances in data science, trends and applications

Artificial intelligence and all its supporting tools, e.g. machine and deep learning in computational intelligence-based systems, are rebuilding our society (economy, education, life-style, etc.) and promising a new era for the social welfare state. In this paper we summarize recent advances in data science and artificial intelligence within the interplay between natural and artificial computation. A review of recent works published in the latter field and the state the art are summarized in a comprehensive and self-contained way to provide a baseline framework for the international community in artificial intelligence. Moreover, this paper aims to provide a complete analysis and some relevant discussions of the current trends and insights within several theoretical and application fields covered in the essay, from theoretical models in artificial intelligence and machine learning to the most prospective applications in robotics, neuroscience, brain computer interfaces, medicine and society, in general.BMS - Pfizer(U01 AG024904). Spanish Ministry of Science, projects: TIN2017-85827-P, RTI2018-098913-B-I00, PSI2015-65848-R, PGC2018-098813-B-C31, PGC2018-098813-B-C32, RTI2018-101114-B-I, TIN2017-90135-R, RTI2018-098743-B-I00 and RTI2018-094645-B-I00; the FPU program (FPU15/06512, FPU17/04154) and Juan de la Cierva (FJCI-2017–33022). Autonomous Government of Andalusia (Spain) projects: UMA18-FEDERJA-084. Consellería de Cultura, Educación e Ordenación Universitaria of Galicia: ED431C2017/12, accreditation 2016–2019, ED431G/08, ED431C2018/29, Comunidad de Madrid, Y2018/EMT-5062 and grant ED431F2018/02. PPMI – a public – private partnership – is funded by The Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbott, Biogen Idec, F. Hoffman-La Roche Ltd., GE Healthcare, Genentech and Pfizer Inc

The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer

The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular reasons why the infection is controlled or instead progresses to subsequent stages of tumorigenesis are largely unknown. In this article, we provide the first complete DNA methylomes of double-stranded DNA viruses associated with human cancer that might provide important clues to help us understand the described process. Using bisulfite genomic sequencing of multiple clones, we have obtained the DNA methylation status of every CpG dinucleotide in the genome of the Human Papilloma Viruses 16 and 18 and Human Hepatitis B Virus, and in all the transcription start sites of the Epstein-Barr Virus. These viruses are associated with infectious diseases (such as hepatitis B and infectious mononucleosis) and the development of human tumors (cervical, hepatic, and nasopharyngeal cancers, and lymphoma), and are responsible for 1 million deaths worldwide every year. The DNA methylomes presented provide evidence of the dynamic nature of the epigenome in contrast to the genome. We observed that the DNA methylome of these viruses evolves from an unmethylated to a highly methylated genome in association with the progression of the disease, from asymptomatic healthy carriers, through chronically infected tissues and pre-malignant lesions, to the full-blown invasive tumor. The observed DNA methylation changes have a major functional impact on the biological behavior of the viruses

DECISION TREE-BASED CONTEXT DEPENDENT SUBLEXICAL UNITS FOR CONTINUOUS SPEECH RECOGNITION OF BASQUE

This paper presents a new methodology, based on the classical decision trees, to get a suitable set of context dependent sublexical units for Basque Continuous Speech Recognition (CSR). The original method proposed by Bahl [1] was applied as the benchmark. Then two new features were added: a data massaging to emphasise the data and a fast and efficient Growing and Pruning algorithm for DT construction. In addition, the use of the new context dependent units to build word models was addressed. The benchmark Bahl approach gave recognition rates clearly outperforming those of context independent phone-like units. Finally the new methodology improves over the benchmark DT approach

Análisis macrosísmico de los efectos geológicos producidos por el terremoto de Lorca 2011 (5,1 Mw): aplicación de la escala ESI-07

256 procesos de ladera ocurrieron como consecuencia del terremoto de Lorca de 2011 (5,1 Mw). La mayor parte son procesos de caídas y avalanchas de rocas con volúmenes máximos que alcanzaron los 1000 m3 en 11 casos. El análisis “Box-counting” de estos procesos indica que el área total afectada por los mismos es de 135 km2, pero solo 85 km2 contienen al menos un caso. Los procesos de mayores dimensiones se registraron en los principales relieves estructurales, paredes de ramblas y zonas de badlands de la zona, pero se identifica una zona de ca. 9-10 km2 en el área epicentral (Barranco Hondo) en la que ocurrieron el 23% de los casos. El análisis permite delinear zonas de intensidades en zonas escasamente pobladas desprovistas de datos EMS, e identifica una intensidad máxima VIII ESI-07256 slope movements were triggered during the 2011 Lorca earthquake (Mw 5.1). They mainly are rock falls and rock avalanches with maximum volumes of 1000 m3 for 11 cases. Box counting analysis indicate that the total area affected by slope movements is of 135 km2, but only 85 km2 contain recorded events. The larger slope movement occurred along the main structural reliefs, deep rambla-valleys, and badlands of the zone. Box-counting also identifies a zone of ca. 9-10 km2 in the epicentral area (Barranco Hondo) in which about the 23%of the cases occurred.The performed analysis allows to delineate and refine the intensity zones in sparsely populated zones without EMS intensity data, identifying VIII ESI-07 intensity from secondary and primary earthquake environmental effects, no detected in previous macroseismic analyses of the zon

Deficient adaptation to centrosome duplication defects in neural progenitors causes microcephaly and subcortical heterotopias.

Congenital microcephaly (MCPH) is a neurodevelopmental disease associated with mutations in genes encoding proteins involved in centrosomal and chromosomal dynamics during mitosis. Detailed MCPH pathogenesis at the cellular level is still elusive, given the diversity of MCPH genes and lack of comparative in vivo studies. By generating a series of CRISPR/Cas9-mediated genetic KOs, we report here that - whereas defects in spindle pole proteins (ASPM, MCPH5) result in mild MCPH during development - lack of centrosome (CDK5RAP2, MCPH3) or centriole (CEP135, MCPH8) regulators induces delayed chromosome segregation and chromosomal instability in neural progenitors (NPs). Our mouse model of MCPH8 suggests that loss of CEP135 results in centriole duplication defects, TP53 activation, and cell death of NPs. Trp53 ablation in a Cep135-deficient background prevents cell death but not MCPH, and it leads to subcortical heterotopias, a malformation seen in MCPH8 patients. These results suggest that MCPH in some MCPH patients can arise from the lack of adaptation to centriole defects in NPs and may lead to architectural defects if chromosomally unstable cells are not eliminated during brain development

Downregulation of specific FBXW7 isoforms with differential effects in T-cell lymphoblastic lymphoma

FBXW7 is a driver gene in T-cell lymphoblastic neoplasia acting through proteasome degradation of key proto-oncogenes. FBXW7 encodes three isoforms, α, β and γ, which differ only in the N-terminus. In this work, massive sequencing revealed significant downregulation of FBXW7 in a panel of primary T-cell lymphoblastic lymphomas characterised by the absence of mutations in its sequence. We observed that decreased expression mainly affected the FBXW7β isoform and to a lesser extent FBXW7α and may be attributed to the combined effect of epigenetic changes, alteration of upstream factors and upregulation of miRNAs. Transient transfections with miRNA mimics in selected cell lines resulted in a significant decrease of total FBXW7 expression and its different isoforms separately, with the consequent increment of critical substrates and the stimulation of cell proliferation. Transient inhibition of endogenous miRNAs in a T-cell lymphoblastic-derived cell line (SUP-T1) was capable of reversing these proliferative effects. Finally, we show how FBXW7 isoforms display different roles within the cell. Simultaneous downregulation of the α and γ isoforms modulates the amount of CCNE1, whilst the β-isoform alone was found to have a prominent role in modulating the amount of c-MYC. Our data also revealed that downregulation of all isoforms is a sine qua non condition to induce a proliferative pattern in our cell model system. Taking these data into account, potential new treatments to reverse downregulation of all or a specific FBXW7 isoform may be an effective strategy to counteract the proliferative capacity of these tumour cells.Spanish Ministry of Economy and Competitiveness (SAF2015-70561-R; MINECO/FEDER, EU; BES-2013-065740); the Autonomous Community of Madrid, Spain (B2017/BMD-3778; LINFOMAS-CM); the Spanish Association against Cancer (AECC, 2018; PROYE18054PIRI) and the Instituto de Salud Carlos III (ISCIII) (ACCI-CIBERER-17). Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged.Peer reviewe