Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

The genus Flavivirus comprises a large number of small, positive-sense single-stranded, RNA viruses able to replicate in the cytoplasm of certain arthropod and/or vertebrate host cells. The genus, which has some 70 member species, includes a number of emerging and re-emerging pathogens responsible for outbreaks of human disease around the world, such as the West Nile, dengue, Zika, yellow fever, Japanese encephalitis, St. Louis encephalitis, and tick-borne encephalitis viruses. Like other RNA viruses, flaviviruses have a compact RNA genome that efficiently stores all the information required for the completion of the infectious cycle. The efficiency of this storage system is attributable to supracoding elements, i.e., discrete, structural units with essential functions. This information storage system overlaps and complements the protein coding sequence and is highly conserved across the genus. It therefore offers interesting potential targets for novel therapeutic strategies. This review summarizes our knowledge of the features of flavivirus genome functional RNA domains. It also provides a brief overview of the main achievements reported in the design of antiviral nucleic acid-based drugs targeting functional genomic RNA elements.Work in our laboratory is supported by the Spanish Ministerio de Economía y Competitividad (BFU2012-31213 and BFU2015-64359-P) and the Consejería de Economía Innovación, Ciencia y Empleo, Junta de Andalucía (CVI-7430). It is also partially funded by FEDER funds from the EU.The authors also acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewedPeer Reviewe

Choline kinase inhibitors EB-3D and EB-3P interferes with lipid homeostasis in HepG2 cells

A full understanding of the molecular mechanism of action of choline kinase α (ChoKα) inhibitors at the cell level is essential for developing therapeutic and preventive approaches for cancer. The aim of the present study was to evaluate the effects of the ChoKα inhibitors EB-3D and EB-3P on lipid metabolism in HepG2 cells. We used [methyl-14C]choline, [1,2-14C]acetic acid and [2-3H]glycerol as exogenous precursors of the corresponding phospholipids and neutral lipids. [Methyl-14C]choline was also used to determine choline uptake. Protein levels were determined by Western blot. Ultrastructural alterations were investigated by transmission electron microscopy. In this work, we demonstrate that EB-3D and EB-3P interfere with phosphatidylcholine biosynthesis via both CDP-choline pathway and choline uptake by the cell. Moreover, the synthesis of both diacylglycerols and triacylglycerols was affected by cell exposure to both inhibitors. These effects were accompanied by a substantial decrease in cholesterol biosynthesis, as well as alterations in the expression of proteins related to cholesterol homeostasis. We also found that EB-3D and EB-3P lowered ChoKα protein levels. All these effects could be explained by the modulation of the AMP-activated protein kinase signalling pathway. We show that both inhibitors cause mitochondrial alteration and an endoplasmic reticulum stress response. EB-3D and EB-3P exert effects on ChoKα expression, AMPK activation, apoptosis, endoplasmic reticulum stress and lipid metabolism. Taken together, results show that EB-3D and EB-3P have potential anticancer activity through the deregulation of lipid metabolism.This work was aided by the Andalusian Regional Government (P11-CVI-7859). The inhibitors were developed under the Cei-Biotic Project CEI2013-MP-1 (University of Granada)

The neandertal group of El Sidrón Cave (Piloña. Asturias. Spain)

572 pp.[EN] From the results obtained we verify that the conjectural late Roman form *situlone, linked to the water, prove the El Sidrón place name, and show that a Neandertal group cannibalised other group make up at least by 13 individuals linked and the fossil remains and the lithic artefacts used were settled in some passage or upper gallery of the karstic system. Few time after the cannibalisation, a high energy process have introduced very quickly those remains being captured in the speleothems of a little gallery. 49 000 years BP ago some classic Neandertals wandered through the actually named concejo of Piloña offering a really interesting information, someone pioneer, in different palaeobiological, paleogenomic, and cultural matters, that offers a more complex and updated vision of that specie. Somebody were redhead, they lived in a smoky atmosphere, they medicate, they have congenital anomalies, they were 1,64 m tall in average, they had a mixed meat and vegetal diet, knap their artefacts with a local flint and, among many other things, they hybridize with Homo sapiens in the Near East.[ES] A partir de los resultados obtenidos comprobamos que la forma conjetural tardorromana *situlone, vinculada al agua, justifica el topónimo El Sidrón. Dichos resultados muestran que un grupo neandertal canibalizó a otro grupo compuesto al menos por 13 individuos emparentados y los restos óseos e instrumentos líticos utilizados se depositaron en algún conducto o galería superior del sistema kárstico. Habiendo pasado muy poco tiempo tras dicha canibalización, un proceso de alta energía introdujo a toda velocidad esos materiales, que permanecieron atrapados entre los espeleotemas de una pequeña galería. Hace unos 49 000 años antes del presente, deambulaban unos neandertales clásicos por el hoy llamado concejo de Piloña, que nos han brindado una muy interesante información, alguna pionera, en diferentes aspectos paleobiológicos, paleogenómicos y culturales, que ofrece una visión renovada y más completa de esta especie. Algunos eran pelirrojos, vivían en un ambiente de humo, se medicaban, tenían varias anomalías congénitas, medían 1,64 m de media, tenían una dieta mixta cárnica y vegetal, tallaban sus herramientas con un sílex local y, entre otras muchas cosas, se hibridaron con la especie Homo Sapiens en Próximo Oriente.Peer reviewe

Acceptance of living liver donation among medical students: A multicenter stratified study from Spain

AIM: To analyze the attitude of Spanish medical students toward living liver donation (LLD) and to establish which factors have an influence on this attitude. METHODS: STUDY TYPE: A sociological, interdisciplinary, multicenter and observational study. STUDY POPULATION: Medical students enrolled in Spain (n = 34000) in the university academic year 2010-2011. SAMPLE SIZE: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire (PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. STATISTICAL ANALYSIS: Student´s t test, ?(2) test and logistic regression analysis. RESULTS: The completion rate was 95.7% (n = 9275). 89% (n = 8258) were in favor of related LLD, and 32% (n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude: (1) age (P = 0.008); (2) sex (P < 0.001); (3) academic year (P < 0.001); (4) geographical area (P = 0.013); (5) believing in the possibility of needing a transplant oneself in the future (P < 0.001); (6) attitude toward deceased donation (P < 0.001); (7) attitude toward living kidney donation (P < 0.001); (8) acceptance of a donated liver segment from a family member if one were needed (P < 0.001); (9) having discussed the subject with one's family (P < 0.001) and friends (P < 0.001); (10) a partner's opinion about the subject (P < 0.001); (11) carrying out activities of an altruistic nature; and (12) fear of the possible mutilation of the body after donation (P < 0.001). CONCLUSION: Spanish medical students have a favorable attitude toward LLD

RepeatsDB in 2021: Improved data and extended classification for protein tandem repeat structures

The RepeatsDB database (URL: https://repeatsdb.org/) provides annotations and classification for protein tandem repeat structures from the Protein Data Bank (PDB). Protein tandem repeats are ubiquitous in all branches of the tree of life. The accumulation of solved repeat structures provides new possibilities for classification and detection, but also increasing the need for annotation. Here we present RepeatsDB 3.0, which addresses these challenges and presents an extended classification scheme. The major conceptual change compared to the previous version is the hierarchical classification combining top levels based solely on structural similarity (Class > Topology > Fold) with two new levels (Clan > Family) requiring sequence similarity and describing repeat motifs in collaboration with Pfam. Data growth has been addressed with improved mechanisms for browsing the classification hierarchy. A new UniProt-centric view unifies the increasingly frequent annotation of structures from identical or similar sequences. This update of RepeatsDB aligns with our commitment to develop a resource that extracts, organizes and distributes specialized information on tandem repeat protein structures.Fil: Paladin, Lisanna. Università di Padova; ItaliaFil: Bevilacqua, Martina. Università di Padova; ItaliaFil: Errigo, Sara. Università di Padova; ItaliaFil: Piovesan, Damiano. Università di Padova; ItaliaFil: Mičetić, Ivan. Università di Padova; ItaliaFil: Necci, Marco. Università di Padova; ItaliaFil: Monzon, Alexander Miguel. Università di Padova; ItaliaFil: Fabre, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; ArgentinaFil: López, José Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; ArgentinaFil: Nilsson, Juliet Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; ArgentinaFil: Ríos, Javier Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Lorenzano Menna, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Cabrera, Maia Diana Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: González Buitrón, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Gonçalves Kulik, Mariane. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Fernández Alberti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Fornasari, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Lagares, Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Biológicas; ArgentinaFil: Hirsh, Layla. Pontificia Universidad Católica de Perú; PerúFil: Andrade Navarro, Miguel A.. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Kajava, Andrey V. Centre National de la Recherche Scientifique; FranciaFil: Tosatto, Silvio C E. Università di Padova; Itali

Al margen. Reflexiones en torno a la imagen

Colección de textos de investigación en torno a la imagen fija y la imagen en movimiento

El grupu neandertal de la Cueva d' El Sidrón (Borines, Piloña)

El artículo está en la lengua asturianaPeer reviewe

Water, El Sidrón Cave (Piloña, Asturias, Spain) and the Neandertal species

En el singular yacimiento de El Sidrón se han producido una impactante serie de acontecimientos relacionados con las actividades y comportamientos de la especie neandertal, integradas en unos procesos del medio físico peculiares, sazonadas con la proximidad de la mejor materia prima silícea asturiana, y con un peculiar encadenamiento de situaciones expeditivas y rápidas. Todo ello integrado en una investigación interdisciplinar.At the unique site of El Sidrón there have been an impressive series of events related to the activities and behaviors of the Neandertal species, integrated into peculiar environmental processes, seasoned with the proximity of the best Asturian siliceous raw material, and with a peculiar chain of expeditious and fast situations. All this integrated into an interdisciplinary investigation

The OpenMolcas Web: A Community-Driven Approach to Advancing Computational Chemistry

The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection