SARS-CoV-2: Evolution and Emergence of New Viral Variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for the coronavirus disease 2019 (COVID-19). The high rate of mutation of this virus is associated with a quick emergence of new viral variants that have been rapidly spreading worldwide. Several mutations have been documented in the receptor-binding domain (RBD) of the viral spike protein that increases the interaction between SARS-CoV-2 and its cellular receptor, the angiotensin-converting enzyme 2 (ACE2). Mutations in the spike can increase the viral spread rate, disease severity, and the ability of the virus to evade either the immune protective responses, monoclonal antibody treatments, or the efficacy of current licensed vaccines. This review aimed to highlight the functional virus classification used by the World Health Organization (WHO), Phylogenetic Assignment of Named Global Outbreak (PANGO), Global Initiative on Sharing All Influenza Data (GISAID), and Nextstrain, an open-source project to harness the scientific and public health potential of pathogen genome data, the chronological emergence of viral variants of concern (VOCs) and variants of interest (VOIs), the major findings related to the rate of spread, and the mutations in the spike protein that are involved in the evasion of the host immune responses elicited by prior SARS-CoV-2 infections and by the protection induced by vaccination.

Clinical pathology, diagnostic and treatment in SARS-CoV-2 infection. / Patología clínica, diagnóstico y tratamiento en la infección por SARS-CoV-2.

SARS-CoV-2 is a new virus causing an infection and illness referred to as COVID-19. As of July 7th of 2020, this virus has been associated worldwide with over 12 million of infections and more than 550,000 deaths. Transmission rate of SARS-CoV-2 in the population is high, and the origin of this coronavirus appears to be related to some species of the bat. However, scientific information related to the pathogenesis, and immune response to COVID-19 changes rapidly, which is why the aim of this work is to provide recent information related to an exacerbated inflammatory immune response which causes multiorgan failure and patient death. The timely identification of infected individuals will be key to stop the spread of infection and in severe cases to establish optimal strategies to reduce the risk of death in critically ill patients. In this review, we have considered the latest findings collected from the clinical studies, diagnostic tests, and treatment for COVID-19. Information presented here will help to the better understanding of this disease.

El SARS-CoV-2 es un nuevo virus que causa la enfermedad denominada COVID-19. Este virus ha generado hasta el 7 de julio de 2020 12 millones de contagios y más de 550 000 muertes en todo el mundo. Se sabe que la tasa de transmisión es muy alta y su origen está relacionado con una especie del murciélago. Sin embargo, la información científica relacionada con la COVID-19 cambia rápidamente, por lo que este trabajo tiene como objetivo aportar información reciente y relacionada con el desarrollo de la respuesta inflamatoria exacerbada, que con frecuencia causa falla orgánica múltiple y muerte del paciente. La rápida identificación de los individuos infectados es clave para detener la propagación de esta enfermedad y en los casos más graves establecer estrategias que permitan la reducción de la infección y del riesgo de muerte. En esta revisión, hemos considerado los últimos hallazgos recopilados de los estudios clínicos, pruebas diagnósticas y de tratamiento para COVID-19. La información presentada en este trabajo contribuirá al entendimiento de esta enfermedad.

Heart myxoma develops oncogenic and metastatic phenotype.

PURPOSE: Heart myxomas have been frequently considered as benign lesions associated with Carney's complex. However, after surgical removal, myxomas re-emerge causing dysfunctional heart. METHODS: To identify whether cardiac myxomas may develop a metastatic phenotype as occurs in malignant cancers, a profile of several proteins involved in malignancy such as oncogenes (c-MYC, K-RAS and H-RAS), cancer-associated metabolic transcriptional factors (HIF-1α, p53 and PPAR-γ) and epithelial-mesenchymal transition proteins (fibronectin, vimentin, ß-catenin, SNAIL and MMP-9) were evaluated in seven samples from a cohort of patients with atrial and ventricular myxomas. The analysis was also performed in: (1) cardiac tissue surrounding the area where myxoma was removed; (2) non-cancer heart tissue (NCHT); and (3) malignant triple negative breast cancer biopsies for comparative purposes. RESULTS: Statistical analysis applying univariate (Kruskal-Wallis and Dunn's tests) and multivariate analyses (PCA, principal component analysis) revealed that heart myxomas (7-15 times) and myxoma surrounding tissue (22-99 times) vs. NCHT showed high content of c-MYC, p53, vimentin, and HIF-1α, indicating that both myxoma and its surrounding area express oncogenes and malignancy-related proteins as occurs in triple negative breast cancer. CONCLUSIONS: Based on ROC (receiver operating characteristics) statistical analysis, c-MYC, HIF-1α, p53, and vimentin may be considered potential biomarkers for malignancy detection in myxoma.

NRP1-positive lung cancer cells possess tumor-initiating properties.

Tumor-initiating cells possess the capacity for self-renewal and to create heterogeneous cell lineages within a tumor. Therefore, the identification and isolation of cancer stem cells is an essential step in the analysis of their biology. The aim of the present study was to determine whether the cell surface protein neuropilin 1 (NRP1) can be used as a biomarker of stem-like cells in lung cancer tumors. For this purpose, NRP1-negative (NRP1-) and NRP1-positive (NRP1+) cell subpopulations from two lung cancer cell lines were sorted by flow cytometry. The NRP1+ cell subpopulation showed an increased expression of pluripotency markers OCT-4, Bmi-1 and NANOG, as well as higher cell migration, clonogenic and self-renewal capacities. NRP1 gene knockdown resulted not only in a decreased expression of stemness markers but also in a decrease in the clonogenic, cell migration and self-renewal potential. In addition, the NRP1+ cell subpopulation exhibited dysregulated expression of epithelial-to-mesenchymal transition-associated genes, including the ΔNp63 isoform protein, a previously reported characteristic of cancer stem cells. Notably, a genome-wide expression analysis of NRP1-knockdown cells revealed a potential new NRP1 pathway involving OLFML3 and genes associated with mitochondrial function. In conclusion, we demonstrated that NRP1+ lung cancer cells have tumor-initiating properties. NRP1 could be a useful biomarker for tumor-initiating cells in lung cancer tumors.

Evaluation of Inulin Replacing Chitosan in a Polyurethane/Polysaccharide Material for Pb2+ Removal.

Downstream waste from industry and other industrial processes could increase concentration of heavy metals in water. These pollutants are commonly removed by adsorption because it is an effective and economical method. Previously, we reported adsorption capacity of a chitosan/polyurethane/titanium dioxide (TiO2) composite for three ions in a dynamic wastewater system. There, increasing the chitosan concentration in composite increased the cation removal as well; however, for ratios higher than 50% of chitosan/TiO2, the manufacturing cost increased significantly. In this work, we address the manufacturing cost problem by proposing a new formulation of the composite. Our hypothesis is that inulin could replace chitosan in the composite formulation, either wholly or in part. In this exploratory research, three blends were prepared with a polyurethane matrix using inulin or/and chitosan. Adsorption was evaluated using a colorimetric method and the Langmuir and Freundlich models. Fourier-transform infrared spectroscopy (FTIR) spectra, scanning electron microscopy (SEM) micrographs, differential scanning calorimetry and thermogravimetric analysis curves were obtained to characterize blends. Results indicate that blends are suitable for toxic materials removal (specifically lead II, Pb2+). Material characterization indicates that polysaccharides were distributed in polyurethane's external part, thus improving adsorption. Thermal degradation of materials was found above 200 °C. Comparing the blends data, inulin could replace chitosan in part and thereby improve the cost efficiency and scalability of the production process of the polyurethane based-adsorbent. Further research with different inulin/chitosan ratios in the adsorbent and experiments with a dynamic system are justified.

NF-κB Participates in the Stem Cell Phenotype of Ovarian Cancer Cells.

BACKGROUND: NF-κB is a transcription factor involved in cancer stem cells maintenance of many tumors. Little is known about the specific stem-associated upstream regulators of this pathway in ovarian cancer. The Aim of the study was to analyze the role of the canonical and non-canonical NF-κB pathways in stem cells of ovarian cancer cell lines. METHODS: Stem cells were isolated using sorting cytometry. Western blot and RT-PCR were used to quantify protein and messenger RNA levels. Loss and gain of function assays were performed using siRNAs and dominant-negative proteins, respectively. NF-κB binding activity was measured with a reporter gene assay. The stem phenotype was estimated with clonogenic assays using soft agar, colony formation, ovospheres formation and in vivo tumorigenicity assays. RESULTS: The CD44+ subpopulation of SKOV3 ovarian cancer cell line presented higher mRNA levels of key stemness genes, an increased tumorigenic capacity and higher expression of the RelA, RelB and IKKα. When the canonical pathway was inhibited by means of a dominant-negative version of IkBα, the stem cell population was reduced, as shown by a reduced CD44+ subpopulation, a decrease in the expression of the stemness genes and a reduction of the stem phenotype. In addition, IKKα, the main upstream non-canonical kinase, was highly expressed in the CSC population. Accordingly, when IKKα was inhibited using shRNAs, the expression of the stemness genes was reduced. CONCLUSIONS: This report is the first to show the importance of several elements of both NF-κB pathway in maintaining the ovarian cancer stem cell population.

NF-kappaΒ-inducing kinase regulates stem cell phenotype in breast cancer.

Breast cancer stem cells (BCSCs) overexpress components of the Nuclear factor-kappa B (NF-κB) signaling cascade and consequently display high NF-κB activity levels. Breast cancer cell lines with high proportion of CSCs exhibit high NF-κB-inducing kinase (NIK) expression. The role of NIK in the phenotype of cancer stem cell regulation is poorly understood. Expression of NIK was analyzed by quantitative RT-PCR in BCSCs. NIK levels were manipulated through transfection of specific shRNAs or an expression vector. The effect of NIK in the cancer stem cell properties was assessed by mammosphere formation, mice xenografts and stem markers expression. BCSCs expressed higher levels of NIK and its inhibition through small hairpin (shRNA), reduced the expression of CSC markers and impaired clonogenicity and tumorigenesis. Genome-wide expression analyses suggested that NIK acts on ERK1/2 pathway to exert its activity. In addition, forced expression of NIK increased the BCSC population and enhanced breast cancer cell tumorigenicity. The in vivo relevance of these results is further supported by a tissue microarray of breast cancer samples in which we observed correlated expression of Aldehyde dehydrogenase (ALDH) and NIK protein. Our results support the essential involvement of NIK in BCSC phenotypic regulation via ERK1/2 and NF-κB.

Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding.

XAF1 is a tumour suppressor gene that compromises cell viability by modulating different cellular events such as mitosis, cell cycle progression and apoptosis. In cancer, the XAF1 gene is commonly silenced by CpG-dinucleotide hypermethylation of its promoter. DNA demethylating agents induce transcriptional reactivation of XAF1, sensitizing cancer cells to therapy. The molecular mechanisms that mediate promoter CpG methylation have not been previously studied. Here, we demonstrate that CTCF interacts with the XAF1 promoter in vivo in a methylation-sensitive manner. By transgene assays, we demonstrate that CTCF mediates the open-chromatin configuration of the XAF1 promoter, inhibiting both CpG-dinucleotide methylation and repressive histone posttranslational modifications. In addition, the absence of CTCF in the XAF1 promoter inhibits transcriptional activation induced by well-known apoptosis activators. We report for the first time that epigenetic silencing of the XAF1 gene is a consequence of the loss of CTCF binding.

Ectopic expression of new alternative splice variant of Smac/DIABLO increases mammospheres formation.

Smac-α is a mitochondrial protein that, during apoptosis, is translocated to the cytoplasm, where it negatively regulates members of the inhibitor of apoptosis (IAP) family via the IAP-binding motif (IBM) contained within its amino-terminus. Here, we describe a new alternative splice variant from Smac gene, which we have named Smac-ε. Smac-ε lacks both an IBM and a mitochondrial-targeting signal (MTS) element. Smac-ε mRNA exhibits a tissue-specific expression pattern in healthy human tissues as well as in several cancer cell lines. The steady-state levels of endogenous Smac-ε protein is regulated by the proteasomal pathway. When ectopically expressed, this isoform presents a cytosolic localization and is unable to associate with or to regulate the expression of X-linked Inhibitor of apoptosis protein, the best-studied member of IAP family. Nevertheless, over-expression of Smac-ε increases mammosphere formation. Whole genome expression analyses from these mammospheres show activation of several pro-survival and growth pathways, including Estrogen-Receptor signaling. In conclusion, our results support the functionality of this new Smac isoform.

Desarrollo tecnológico para el mejoramiento de la comunicación a distancia entre personas con discapacidad / Technological development for improving long-distance communication between handicapped people

Objetivo Proporcionar a la población en general, especialmente a las personas en situación de discapacidad, un dispositivo de comunicación que mediante: 1) Un proceso inteligente; 2) Un sistema codificación/decodificación adaptativo y 3) Unas interfaces accesibles, les permita fomentar unas adecuadas competencias comunicativas, como mecanismo de inclusión social, aportándoles las posibilidades de satisfacer adecuadamente algunas necesidades humanas fundamentales. Métodos La investigación se realizó con base en tres enfoques, cada uno predecesor del siguiente, inicialmente el exploratorio, con el que se buscó determinar el estado del arte de la investigación, luego el descriptivo, que buscó profundizar en la tecnología desarrollada o aplicada a la inclusión social de las personas con discapacidad, y finalmente uno de tipo cuasi-experimental, con el que se desarrolló un producto tecnológico que fue validado con personas de distintas discapacidades, realizando los ajustes y adaptaciones necesarias. Resultados El principal resultado de este proyecto fue la creación de un dispositivo de comunicación que incrementa el desarrollo de las competencias comunicativas en las personas con discapacidad motora, ciego, sordo postlingual bilingüe y sordociego postlingual, entre ellas y/o cualquier otra persona sin discapacidad, sin que esta última deba tener también el dispositivo diseñado y construido en esta investigación. Conclusiones Se diseñó, implementó y validó el desarrollo de un dispositivo tecnológico denominado como prototipo SCDA, basado en funciones electrónicas que le permiten al usuario el desarrollo de algunas necesidades humanas fundamentales, basadas en el derecho inherente que todo ser humano sin importar su condición física, mental o económica tiene de comunicarse.

Objective Providing the general public, especially people suffering from disabilities, with a communication device promoting appropriate communication skills by using a smart, adaptive encoding/decoding system having accessible interfaces as a mechanism of social inclusion, thereby providing suitable opportunities for meeting some basic human needs. Methods The research was based on three stages, each preceding the next. It began with an exploratory stage which sought to determine the state of the art regarding research. It was followed by a descriptive one which sought to further the technology developed or applied to the social inclusion of handicapped people. The last stage was quasi-experimental which developed a technological product which was validating with people having different disabilities, the necessary adjustments and adaptations then being made. Results This project's main result lay in creating a communication device which increased the development of communication skills in people suffering from motor disabilities or who were blind, postlingually deaf and postlingually deaf-blind and/or any other person without disability (the latter group having a device designed and constructed during this investigation). Conclusions A technological device called the SCDA prototype was designed, implemented and validated; it was based on electronic functions allowing the user to develop some basic human needs, based on every human being's inherent right to communicate, regardless of their physical, mental or economic condition.

[Technological development for improving long-distance communication between handicapped people]. / Desarrollo tecnológico para el mejoramiento de la comunicación a distancia entre personas con discapacidad.

OBJECTIVE: Providing the general public, especially people suffering from disabilities, with a communication device promoting appropriate communication skills by using a smart, adaptive encoding/decoding system having accessible interfaces as a mechanism of social inclusion, thereby providing suitable opportunities for meeting some basic human needs. METHODS: The research was based on three stages, each preceding the next. It began with an exploratory stage which sought to determine the state of the art regarding research. It was followed by a descriptive one which sought to further the technology developed or applied to the social inclusion of handicapped people. The last stage was quasi-experimental which developed a technological product which was validating with people having different disabilities, the necessary adjustments and adaptations then being made. RESULTS: This project's main result lay in creating a communication device which increased the development of communication skills in people suffering from motor disabilities or who were blind, postlingually deaf and postlingually deaf-blind and/or any other person without disability (the latter group having a device designed and constructed during this investigation). CONCLUSIONS: A technological device called the SCDA prototype was designed, implemented and validated; it was based on electronic functions allowing the user to develop some basic human needs, based on every human being's inherent right to communicate, regardless of their physical, mental or economic condition.