Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas.

Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.

Death-seq identifies regulators of cell death and senolytic therapies.

Selectively ablating damaged cells is an evolving therapeutic approach for age-related disease. Current methods for genome-wide screens to identify genes whose deletion might promote the death of damaged or senescent cells are generally underpowered because of the short timescales of cell death as well as the difficulty of scaling non-dividing cells. Here, we establish "Death-seq," a positive-selection CRISPR screen optimized to identify enhancers and mechanisms of cell death. Our screens identified synergistic enhancers of cell death induced by the known senolytic ABT-263. The screen also identified inducers of cell death and senescent cell clearance in models of age-related diseases by a related compound, ABT-199, which alone is not senolytic but exhibits less toxicity than ABT-263. Death-seq enables the systematic screening of cell death pathways to uncover molecular mechanisms of regulated cell death subroutines and identifies drug targets for the treatment of diverse pathological states such as senescence, cancer, and fibrosis.

Frequency of allergic reactions in egg allergic patients after receiving the yellow fever vaccine.

BACKGROUND: Immunization with live attenuated viral yellow fever vaccine (YFV) grants effective immunity in most cases, and is recommended and prioritized for residents and travelers of endemic countries. YFV is seldom administered to egg-allergic patients (EAP) since it is cultivated in embryonated chicken eggs and may contain residual egg proteins, being a problem for egg-allergic residents and travelers of endemic countries. OBJECTIVE: Describe the frequency of allergic reactions after YFV administration in confirmed EAP from an allergy outpatient center in Bogotá, Colombia. METHODS: An observational, retrospective, cross-sectional, and descriptive study was conducted from January 2017 to December 2019. EAP whose allergy was confirmed with a positive Skin Prick Test (SPT) and/or egg protein-specific IgE levels who hadn't received the YFV were included. Every patient had an SPT, severe EAP, and an additional Intradermal Test (IDT) done with the vaccine. If the vaccine SPT and IDT were negative, the YFV was administered as a single dose; if either were positive, the YFV was administered in graded doses. Statistical analysis was done in Stata16MP. RESULTS: Seventy one patients were included, 24 (33.8%) of those had a history of egg anaphylaxis. All patients had negative YFV SPTs, and two of the five YVF IDTs were positive. Two patients, with previous egg-anaphylaxis, presented allergic reactions to the vaccine. CONCLUSIONS: YFV did not trigger allergic reactions in EAP without history of egg-anaphylaxis. With further research, safe single-dose vaccination to this population could be considered; however, patients with previous egg-anaphylaxis should be evaluated by an allergist before vaccination.

Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging.

Exercise has the ability to rejuvenate stem cells and improve tissue regeneration in aging animals. However, the cellular and molecular changes elicited by exercise have not been systematically studied across a broad range of cell types in stem cell compartments. We subjected young and old mice to aerobic exercise and generated a single-cell transcriptomic atlas of muscle, neural, and hematopoietic stem cells with their niche cells and progeny, complemented by whole transcriptome analysis of single myofibers. We found that exercise ameliorated the upregulation of a number of inflammatory pathways associated with old age and restored aspects of intercellular communication mediated by immune cells within these stem cell compartments. Exercise has a profound impact on the composition and transcriptomic landscape of circulating and tissue-resident immune cells. Our study provides a comprehensive view of the coordinated responses of multiple aged stem cells and niche cells to exercise at the transcriptomic level.

Frequency of allergic reactions in egg allergic patients after receiving the yellow fever vaccine

Background: Immunization with live attenuated viral yellow fever vaccine (YFV) grants effective immunity in most cases, and is recommended and prioritized for residents and travelers of endemic countries. YFV is seldom administered to egg-allergic patients (EAP) since it is cultivated in embryonated chicken eggs and may contain residual egg proteins, being a problem for egg-allergic residents and travelers of endemic countries. Objective: Describe the frequency of allergic reactions after YFV administration in confirmed EAP from an allergy outpatient center in Bogotá, Colombia. Methods: An observational, retrospective, cross-sectional, and descriptive study was conducted from January 2017 to December 2019. EAP whose allergy was confirmed with a positive Skin Prick Test (SPT) and/or egg protein–specific IgE levels who hadn’t received the YFV were included. Every patient had an SPT, severe EAP, and an additional Intradermal Test (IDT) done with the vaccine. If the vaccine SPT and IDT were negative, the YFV was administered as a single dose; if either were positive, the YFV was administered in graded doses. Statistical analysis was done in Stata16MP. Results: Seventy one patients were included, 24 (33.8%) of those had a history of egg anaphylaxis. All patients had negative YFV SPTs, and two of the five YVF IDTs were positive. Two patients, with previous egg-anaphylaxis, presented allergic reactions to the vaccine. Conclusions: YFV did not trigger allergic reactions in EAP without history of egg-anaphylaxis. With further research, safe single-dose vaccination to this population could be considered; however, patients with previous egg-anaphylaxis should be evaluated by an allergist before vaccination (AU)

Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo.

Adult skeletal muscle stem cells (MuSCs) are important for muscle regeneration and constitute a potential source of cell therapy. However, upon isolation, MuSCs rapidly exit quiescence and lose transplantation potency. Maintenance of the quiescent state in vitro preserves MuSC transplantation efficiency and provides an opportunity to study the biology of quiescence. Here we show that Tubastatin A (TubA), an Hdac6 inhibitor, prevents primary cilium resorption, maintains quiescence, and enhances MuSC survival ex vivo. Phenotypic characterization and transcriptomic analysis of TubA-treated cells revealed that TubA maintains most of the biological features and molecular signatures of quiescence. Furthermore, TubA-treated MuSCs showed improved engraftment ability upon transplantation. TubA also induced a return to quiescence and improved engraftment of cycling MuSCs, revealing a potentially expanded application for MuSC therapeutics. Altogether, these studies demonstrate the ability of TubA to maintain MuSC quiescence ex vivo and to enhance the therapeutic potential of MuSCs and their progeny.

Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist.

Skeletal muscle possesses remarkable regenerative ability because of the resident muscle stem cells (MuSCs). A prominent feature of quiescent MuSCs is a high content of heterochromatin. However, little is known about the mechanisms by which heterochromatin is maintained in MuSCs. By comparing gene-expression profiles from quiescent and activated MuSCs, we found that the mammalian Hairless (Hr) gene is expressed in quiescent MuSCs and rapidly down-regulated upon MuSC activation. Using a mouse model in which Hr can be specifically ablated in MuSCs, we demonstrate that Hr expression is critical for MuSC function and muscle regeneration. In MuSCs, loss of Hr results in reduced trimethylated Histone 3 Lysine 9 (H3K9me3) levels, reduced heterochromatin, increased susceptibility to genotoxic stress, and the accumulation of DNA damage. Deletion of Hr leads to an acceleration of the age-related decline in MuSC numbers. We have also demonstrated that despite the fact that Hr is homologous to a family of histone demethylases and binds to di- and trimethylated H3K9, the expression of Hr does not lead to H3K9 demethylation. In contrast, we show that the expression of Hr leads to the inhibition of the H3K9 demethylase Jmjd1a and an increase in H3K9 methylation. Taking these data together, our study has established that Hr is a H3K9 demethylase antagonist specifically expressed in quiescent MuSCs.

Comportamiento del embarazo adolescente en el municipioJatibonico, Sancti Spíritus, Cuba

RESUMEN:Introducción: El embarazo en la adolescencia conlleva el fracaso en la continuidad de los estudios y la preparación para la vida adulta.Objetivo: Analizar el comportamiento del embarazo adolescente en el municipio Jatibonico, Sancti Spíritus, Cuba.Métodos: Se realizó un estudio descriptivo y transversal. El universo estuvo constituido por 125 embarazadas adolescentes del municipio Jatibonico, en la provincia de Sancti Spíritus durante el período comprendido entre 2014 y 2019. Se aplicó un cuestionario y los datos obtenidos se reflejaron en tablas atendiendo a las variables analizadas.Resultados: Predominaron las adolescentes entre 16 y 18 años. La principal causa de embarazo fue el desconocimiento de los métodos anticonceptivos. Los métodos más utilizados fueron el condón y la T de cobre. Las comorbilidades que se presentaron con mayor frecuencia fueron las malformaciones, la anemia y la amenaza de parto pretérmino. La mayoría de las adolescentes embarazadas abandonaron los estudios.Conclusiones: Las comorbilidades más frecuentes fueron las malformaciones,seguidas de la anemia y la amenaza de parto pretérmino. La mayoría de las adolescentes abandonaron los estudios o frustraron sus proyectos de vida.[AU]

Prevalencia de embarazos con infección por virus Zika en una Unidad de Primer Nivel de Atención en Coatzacoalcos Veracruz México del Instituto Mexicano del Seguro Social / PREVALENCE OF PREGNANCIES WITH ZIKA VIRUS INFECTION IN A FIRST LEVEL CARE UNIT IN COATZACOALCOS VERACRUZ MEXICO OF THE MEXICAN INSTITUTE OF SOCIAL SECURITY

El virus Zika, es un arbovirus del género flavivirus (familia Flaviviridae), muy cercano filogenéticamente al del dengue, fiebre amarilla, la encefalitis japonesa, o el virus del Nilo Occidental. El presente estudio exploratorio busca identificar los casos confirmados y sugestivos de infección por virus Zika en mujeres embarazadas en la Unidad de Medicina Familiar N° 60 del IMSS de Coatzacoalcos, Veracruz. México como primera aproximación epidemiológica en esta región.

The Zika virus is an arbovirus of the genus flavivirus (family Flaviviridae), very closely phylogenetically a virus such as dengue fever, yellow fever, Japanese encephalitis, or West Nile virus. According to the Epidemiological Surveillance System for Zíka Virus Disease, until November 4th, 2016, in Mexico there were 6,094 confirmed cases of infection and 3,167 suspected cases of Zika virus infection in pregnant women in 24 states of the Mexican Republic, with a higher prevalence in Veracruz, Chiapas, Colima, Campeche, Yucatan and Quintana Roo. This is an original study that focuses on identifying the confirmed and suggestive cases of Zika virus infection in pregnant women in the Family Medicine Unit No. 60 of the IMSS in Coatzacoalcos, Veracruz. Mexico; It is an exploratory study in the registry of cases of pregnant women with Zika virus infection in the Family Medicine Unit No. 60 of Coatzacoalcos, Veracruz, Mexico as epidemiological basis

Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1.

Aging impairs tissue repair. This is pronounced in skeletal muscle, whose regeneration by muscle stem cells (MuSCs) is robust in young adult animals but inefficient in older organisms. Despite this functional decline, old MuSCs are amenable to rejuvenation through strategies that improve the systemic milieu, such as heterochronic parabiosis. One such strategy, exercise, has long been appreciated for its benefits on healthspan, but its effects on aged stem cell function in the context of tissue regeneration are incompletely understood. Here we show that exercise in the form of voluntary wheel running accelerates muscle repair in old animals and improves old MuSC function. Through transcriptional profiling and genetic studies, we discovered that the restoration of old MuSC activation ability hinges on restoration of Cyclin D1, whose expression declines with age in MuSCs. Pharmacologic studies revealed that Cyclin D1 maintains MuSC activation capacity by repressing TGFß signaling. Taken together, these studies demonstrate that voluntary exercise is a practicable intervention for old MuSC rejuvenation. Furthermore, this work highlights the distinct role of Cyclin D1 in stem cell quiescence.

Seguimiento de hijos de madres con infección por virus ZIKA en una Unidad de Primer Nivel de Atención Médica de Coatzacoalcos Veracruz, México del Instituto Mexicano del Seguro Social / Follow-Up of congenital Zika virus Infection

El virus Zika, es un arbovirus del género flavivirus (familia Flaviviridae), muy cercano filogenéticamente a virus como el dengue, fiebre amarilla, la encefalitis japonesa, o el virus del Nilo Occidental. El presente estudio es de tipo exploratorio con base en el registro de casos de recién nacidos y lactantes hijos de mujeres embarazadas con infección de virus Zika en la Unidad de Medicina Familiar Nº 60 de Coatzacoalcos, Veracruz, dentro del período de diciembre del 2016 a julio del 2017. Se realizó un estudio polietápico que constó de revisión de casos por medio de uso de expediente clínico en la Consulta Externa en la Unidad Médico Familiar Nº 60 del IMSS de Coatzacoalcos, Veracruz. como primera aproximación epidemiológica en esta región en recién nacidos y lactantes hijos de madres con infección por virus Zika, que posteriormente fueron sometidos a estudios de valoración oftalmológica, neurológica y somatométrica; con ayuda del servicio de Salud Pública de dicha unidad (AU)

Zika virus is an arbovirus of the genusflavivirus (family Flaviviridae), very close phylogenetically to viruses such as denque, yellow fever, japanese encephalitis, or West Nile virus. The present study is exploratory based on the registry of cases of newborns and infants born to pregnant women with zika virus infection in the Family Medicine Unit Nº 60 of Coatzacalcos, Veracruz, within the period of December 2016 to July 2017. A multistage study was carried out that consisted of the review of cases through the use of a clinical file in the Outpatient Consultation in the Family Medical Unit Nº 60 of the IMSS. of Coatzacoalcos, Veracruz. As a first epidemiological approach in this region in newborns and infants born to mothers with Zika virus infection, who were subsequently subjected to ophtalmological, neurological and somatometric assessment studies; with the help of the Public Health service of said unit (AU)

Downregulation of Lnc-Spry1 mediates TGF-ß-induced epithelial-mesenchymal transition by transcriptional and posttranscriptional regulatory mechanisms.

Long non-coding RNAs (lncRNAs) are a class of regulatory genes that participate in a wide range of biological processes, including proliferation, differentiation and development, as well as in a broad spectrum of diseases. Although the role of lncRNAs in TGF-ß-induced epithelial-to-mesenchymal transition (EMT) has been well established, little is known about the role of lncRNAs as immediate-early regulators of EMT. Here lnc-Spry1 is identified as an immediate-early regulator of EMT that is downregulated by TGF-ß. It is also found that knockdown of lnc-Spry1 promotes a mesenchymal-like phenotype and results in increased cell migration and invasion. In addition, it is shown that lnc-Spry1 depletion preferentially affects the expression of TGF-ß-regulated gene targets. Moreover, lnc-Spry1 associates with U2AF65 splicing factor, suggesting a role in alternative splicing. Depletion of lnc-Spry1 induces, as TGF-ß, isoform switching of fibroblast growth factor receptors, resulting in FGF-2-sensitive cells. Taken together, these results show that lnc-Spry1 could act as an early mediator of TGF-ß signaling and reveal different roles for a lncRNA in modulating transcriptional and posttranscriptional gene expression.

Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as important factors in anoikis resistance.

MicroRNAs (miRNAs) have been widely studied in order to elucidate their biological functions. MicroRNA microarrays or miRNA overexpression libraries generated by synthesis and cloning of individual miRNAs have been used to study their different roles. In this work, we have developed a novel methodology to express mature miRNAs and other small RNAs from a double convergent RNA polymerase III promoter. We show that the generated miRNAs function similarly to those processed from primary transcripts or pri-miRNAs. This system allowed us to produce a lentiviral library expressing the whole population of small RNAs present in a metastatic cell line. A functional screening using this library led to the identification of hsa-miR-30b and hsa-miR-30c as negative regulators of cell death induced by loss of attachment (anoikis). Importantly, we demonstrated that the acquisition of anoikis resistance via these miRNAs is achieved through down-regulation of caspase 3 expression. Moreover, overexpression of these miRNAs resulted in a decrease of other types of caspase 3-dependent cell death and enhanced the survival of MCF10A acinar cells in morphogenesis assays, suggesting a putative role as oncomirs. In summary, this novel methodology provides a powerful and effective way for identifying novel small RNAs involved in a particular biological process.

Success in chess mediated by mental molds / El éxito en ajedrez explicado por los moldes mentales

Research has revealed the impact of cognitive-affective strategies (Molds of the Mind) on subjective well-being, interpersonal relationships, or school achievement. However, it seems odd that such strategies could influence the success of chess players, because this game is usually considered to be influenced mainly by technical and cognitive skills. To examine the influence of cognitive-affective molds, 53 chess players, ages from 9 to 16 years old, enrolled in sport competitions, were assigned to two groups, high and low success. They responded to the MOLDES, designed to evaluate individuals’ molds. The results show that the «Mental Molds» of the most successful players are more realistic, positive and regulators of the emotions, while the molds of the less successful players are more evasive, magic, defensive and inoperative

La investigación pasada ha demostrado que las estrategias cognitivo-afectivas (Moldes de la Mente) explican, en gran medida, el bienestar subjetivo, las relaciones interpersonales y el rendimiento académico. Por esta razón, parece razonable esperar que tales estrategias deban influir significativamente sobre el éxito de los jugadores de ajedrez, a pesar de la creencia de que este juego está determinado por el uso de habilidades cognitivas y técnicas. Con el fin de examinar esta hipótesis, 53 jugadores de ajedrez, de entre 9 y 16 años, fueron asignados a dos grupos de rendimiento ajedrecístico (alto y bajo), aplicándoseles el cuestionario MOLDES. Los resultados muestran que los Moldes Mentales de los jugadores exitosos son más realistas, positivos y reguladores de las emociones, mientras que los de los jugadores menos exitosos son más evasivos, mágicos, defensivos e inoperantes

Success in chess mediated by mental molds.

Research has revealed the impact of cognitive-affective strategies (Molds of the Mind) on subjective well-being, interpersonal relationships, or school achievement. However, it seems odd that such strategies could influence the success of chess players, because this game is usually considered to be influenced mainly by technical and cognitive skills. To examine the influence of cognitive-affective molds, 53 chess players, ages from 9 to 16 years old, enrolled in sport competitions, were assigned to two groups, high and low success. They responded to the MOLDES, designed to evaluate individuals' molds. The results show that the "Mental Molds" of the most successful players are more realistic, positive and regulators of the emotions, while the molds of the less successful players are more evasive, magical, defensive and inoperative.

The effect of temperature on food emulsifiers at fluid-fluid interfaces.

Heat-induced interfacial aggregation of a whey protein isolate (WPI) with a high content of beta-lactoglobulin (>92%), previously adsorbed at the oil-water interface, was studied by means of interfacial dynamic characteristics performed in an automatic drop tensiometer. Protein concentration in aqueous bulk phase ranging between 1x10(-1) and 1x10(-5) % wt/wt was studied as a variable. The experiments were carried out at temperatures ranging from 20-80 degrees C with different thermal regimes. During the heating period, competition exists between the effect of temperature on the film fluidity and the increase in mechanical properties associated with the interfacial gelation process. Interfacial crystallisation of food polar lipids (monopalmitin, monoolein, and monolaurin) previously adsorbed at the oil-water interface, was studied by interfacial dynamic characteristics (interfacial tension and surface dilational properties). The temperature, ranging between 40 and 2 degrees C, and the lipid concentration in aqueous oil phase, ranging between 1x10(-2) and 1x10(-4) % wt/wt, were studied as variables. Significant changes in interfacial dynamic characteristics associated with interfacial lipid crystallisation were observed as a function of lipid concentration in the bulk phase. Interfacial crystallisation of food polar lipids (monopalmitin, monoolein, and monolaurin) at the air-water interface, was studied by pi-A isotherms performed in a Langmuir trough coupled with Brewster angle microscopy (BAM). A condensation in monoglyceride monolayers towards lower molecular area was observed as the temperature decreased. This effect was attributed to lipid crystallisation at lower temperatures. BAM images corroborated the effect of temperature on the monolayer structure, as a function of the monoglyceride type.