Structural representations of DNA regulatory substrates can enhance sequence-based algorithms by associating functional sequence variants

The nucleotide sequence representation of DNA can be inadequate for resolving protein-DNA binding sites and regulatory substrates, such as those involved in gene expression and horizontal gene transfer. Considering that sequence-like representations are algorithmically very useful, here we fused over 60 currently available DNA physicochemical and conformational variables into compact structural representations that can encode single DNA binding sites to whole regulatory regions. We find that the main structural components reflect key properties of protein-DNA interactions and can be condensed to the amount of information found in a single nucleotide position. The most accurate structural representations compress functional DNA sequence variants by 30% to 50%, as each instance encodes from tens to thousands of sequences. We show that a structural distance function discriminates among groups of DNA substrates more accurately than nucleotide sequence-based metrics. As this opens up a variety of implementation possibilities, we develop and test a distance-based alignment algorithm, demonstrating the potential of using the structural representations to enhance sequence-based algorithms. Due to the bias of most current bioinformatic methods to nucleotide sequence representations, it is possible that considerable performance increases might still be achievable with such solutions.Comment: 20 pages, 8 figures, 3 tables, conferenc

Coronavirus disease 2019 (COVID-19) and human pregnancy: a scoping review

The coronavirus disease 2019 (COVID-19) is caused by the infection with a coronavirus (SARS-CoV-2). Pregnants present mild or moderate symptoms, with 5% presenting as a severe pneumonia. Prevalence and evolution of COVID-19 in pregnancy is similar to that of the general population, including the risk of maternal death. Radiography, computed tomography or ultrasound imaging are pivotal for the diagnosis and given the clinical suspicion of COVID-19 pneumonia. Lab findings include lymphocytopenia, thrombocytopenia, leukopenia, and the elevation of D-dimer and ferritin. To date, there is no specific treatment or vaccination for COVID-19; yet clinical management in pregnants is also similar to that of the general population, with prophylactic antibiotic treatment for bacterial pneumonia and oxygen support. Thromboprophylaxis should be indicated in severe cases, given that pregnancy is a hypercoagulable state that may be exacerbated by COVID-19. Hospital management should focus on treating the mother and protecting the newborn and the health personnel. Regarding COVID-19 and perinatal outcomes, premature deliveries are mainly associated to iatrogenic pregnancy termination through cesarean section aimed conserving maternal well-being. To date, vertical transmission to the fetus has not been demonstrated, neither intrauterine, nor through the birth canal. The virus has not been detected in vaginal fluids, or in breast milk. Breastfeeding may be allowed depending on maternal and neonatal health status. There are still many unknown issues, although there is a continuous update of scientific information related to pregnancy and COVID-19

Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Gioblastoma Multiforme Cells

Ursolic acid (UA) is a bioactive compound which has demonstrated therapeutic efficacy in a variety of cancer cell lines. UA activates various signalling pathways in Glioblastoma multiforme (GBM) and offers a promising starting point in drug discovery; however, understanding the relationship between cell death and migration has yet to be elucidated. UA induces a dose dependent cytotoxic response demonstrated by flow cytometry and biochemical cytotoxicity assays. Inhibitor and fluorescent probe studies demonstrate that UA induces a caspase independent, JNK dependent, mechanism of cell death. Migration studies established that UA inhibits GBM collective cell migration in a time dependent manner that is independent of the JNK signalling pathway. Cytotoxicity induced by UA results in the formation of acidic vesicle organelles (AVOs), speculating the activation of autophagy. However, inhibitor and spectrophotometric analysis demonstrated that autophagy was not responsible for the formation of the AVOs. Confocal microscopy and isosurface visualisation determined co-localisation of lysosomes with the previously identified AVOs, thus providing evidence that lysosomes are likely to be playing a role in UA induced cell death. Collectively, our data identify that UA rapidly induces a lysosomal associated mechanism of cell death in addition to UA acting as an inhibitor of GBM collective cell migration

Learning styles and their relationship with the Technologies of Information and Communication (TIC) in the adaptation of pharmacy studies to the ESHE

Introducción: El conocimiento de los estilos de aprendizaje es fundamental para el docente a fin de comprender cómo aprenden sus alumnos y así modificar/reforzar su estilo de enseñanza. La aplicación de las nuevas Tecnologías de la Comunicación y de la Información (TIC) facilita la adaptación de las enseñanzas universitarias al Espacio Europeo de Educación Superior (EEES). Objetivo: Evaluar el estilo de aprendizaje de los alumnos de Farmacia de la Universidad Complutense de Madrid (UCM) y comparar dichos estilos con las TIC. Metodología: Alumnos de 4º curso de licenciatura en Farmacia y de postgrado. Todos respondieron al cuestionario CHAEA de estilos de aprendizaje. Además, se ha planteado un nuevo cuestionario para correlacionar estilos de aprendizaje y TIC. Discusión: Las puntuaciones positivas más elevadas correspondieron al estilo reflexivo seguido del teórico. Más del 80% de los alumnos muestran preferencia muy elevada por las clases magistrales (puntuaciones 4-5, siendo 5 la puntación de máxima preferencia). Este resultado estaría en concordancia con el estilo mayoritario de aprendizaje de los alumnos evaluados. Más del 90% de los alumnos valora de forma altamente positiva (4-5) la impartición de clases mediante la utilización de presentaciones en PowerPoint y, a continuación la utilización de la pizarra y la proyección de videos. Conclusiones: El estilo de aprendizaje de los alumnos de cuarto curso de Farmacia y de postgrado es fundamentalmente reflexivo aunque valoran de forma altamente positiva la utilización de las TIC, lo que confirma la importancia de su uso en la consecución de los objetivos del EEES.Introduction: knowledge of the learning styles of Pharmacy students is an important tool that can be used to improve teaching thereby reinforcing the use of appropriate and transferable teaching strategies. For this, the use of the Technologies of Information and Communication (TIC) may facilitate the implementation of the European Space for Higher Education (ESHE). Objective: To evaluate the learning styles of graduate and postgraduate pharmacy students at the Universidad Complutense of Madrid and, to compare the student´s learning styles with their preferences regarding the use of the TIC. Methods: The study was performed on fourth-year pharmacy students and postgraduate students. The instrument used to analyze the learning styles was the CHAEA questionnaire. Moreover, a new questionnaire was developed and implemented in order to establish a correlation between learning styles and TIC. Results: The preferred learning styles corresponded to reflexive and, in second place, theoretical learning. More than 80% of the students highly graded traditional lectures (4-5, being 5 the grade for maximum preference), with this result in accordance with the main learning style of the population assayed. More than 90% of the students also positively graded (4-5) multimedia presentations using PowerPoint software, followed by the use of blackboard and videos. Conclusions: The main learning style of fourth-year graduate students and postgraduate students at the School of Pharmacy (UCM) is reflexive. The populations assayed highly and positively graded the use of TIC, thereby stating their importance in the implementation of the ESHE

Identification and Visualization of CD8+ T Cell Mediated IFN-γ Signaling in Target Cells during an Antiviral Immune Response in the Brain

CD8+ T cells infiltrate the brain during an anti-viral immune response. Within the brain CD8+ T cells recognize cells expressing target antigens, become activated, and secrete IFNγ. However, there are no methods to recognize individual cells that respond to IFNγ. Using a model that studies the effects of the systemic anti-adenoviral immune response upon brain cells infected with an adenoviral vector in mice, we describe a method that identifies individual cells that respond to IFNγ. To identify individual mouse brain cells that respond to IFNγ we constructed a series of adenoviral vectors that contain a transcriptional response element that is selectively activated by IFNγ signaling, the gamma-activated site (GAS) promoter element; the GAS element drives expression of a transgene, Cre recombinase (Ad-GAS-Cre). Upon binding of IFNγ to its receptor, the intracellular signaling cascade activates the GAS promoter, which drives expression of the transgene Cre recombinase. We demonstrate that upon activation of a systemic immune response against adenovirus, CD8+ T cells infiltrate the brain, interact with target cells, and cause an increase in the number of cells expressing Cre recombinase. This method can be used to identify, study, and eventually determine the long term fate of infected brain cells that are specifically targeted by IFNγ. The significance of this method is that it will allow to characterize the networks in the brain that respond to the specific secretion of IFNγ by anti-viral CD8+ T cells that infiltrate the brain. This will allow novel insights into the cellular and molecular responses underlying brain immune responses

The ambivalent shadow of the pre-Wilsonian rise of international law

The generation of American international lawyers who founded the American Society of International Law in 1906 and nurtured the soil for what has been retrospectively called a “moralistic legalistic approach to international relations” remains little studied. A survey of the rise of international legal literature in the U.S. from the mid-19th century to the eve of the Great War serves as a backdrop to the examination of the boosting effect on international law of the Spanish American War in 1898. An examination of the Insular Cases before the US Supreme Court is then accompanied by the analysis of a number of influential factors behind the pre-war rise of international law in the U.S. The work concludes with an examination of the rise of natural law doctrines in international law during the interwar period and the critiques addressed.by the realist founders of the field of “international relations” to the “moralistic legalistic approach to international relation

Cold Atmospheric Plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma treated cells that stained positive with acridine orange. Western immunoblotting confirmed that autophagy is not activated following plasma treatment. Acridine orange intensity correlates closely with the lysosomal marker Lyso TrackerTM Deep Red. Further investigation using isosurface visualisation of confocal imaging confirmed that lysosomal accumulation occurs in plasma treated cells. The accumulation of lysosomes was associated with concomitant cell death following plasma treatment. In conclusion, we observed rapid accumulation of acidic vesicles and cell death following CAP treatment in GBM cells. We found no evidence that either apoptosis or autophagy, however, determined that a rapid accumulation of late stage endosomes/lysosomes precedes membrane permeabilisation, mitochondrial membrane depolarisation and caspase independent cell death

An RNA-seq Based Machine Learning Approach Identifies Latent Tuberculosis Patients With an Active Tuberculosis Profile.

A better understanding of the response against Tuberculosis (TB) infection is required to accurately identify the individuals with an active or a latent TB infection (LTBI) and also those LTBI patients at higher risk of developing active TB. In this work, we have used the information obtained from studying the gene expression profile of active TB patients and their infected -LTBI- or uninfected -NoTBI- contacts, recruited in Spain and Mozambique, to build a class-prediction model that identifies individuals with a TB infection profile. Following this approach, we have identified several genes and metabolic pathways that provide important information of the immune mechanisms triggered against TB infection. As a novelty of our work, a combination of this class-prediction model and the direct measurement of different immunological parameters, was used to identify a subset of LTBI contacts (called TB-like) whose transcriptional and immunological profiles are suggestive of infection with a higher probability of developing active TB. Validation of this novel approach to identifying LTBI individuals with the highest risk of active TB disease merits further longitudinal studies on larger cohorts in TB endemic areas