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El linfoma difuso de grandes células B (LDGCB) de cérvix es extremadamente raro. Generalmente es subdiagnosticado debido a que fácilmente es confundido con el carcinoma escamoso de cérvix dado la similitud de los síntomas. Por lo tanto, su diagnóstico representa un desafío. Presentamos el caso de una mujer postmenopáusica con sinusorragia que requirió múltiples biopsias para la confirmación diagnóstica.

Up to now the lipid bilayers were rarely considered as targets in cancer therapy despite pronounced differences in lipid composition between plasma membranes of benign and malignant cells. In this study we demonstrate that the lipid bilayer of the plasma membrane is druggable and suitable for facilitating selective delivery of amphiphilic gemcitabine-squalene nanomedicines to cancer cells. Data from radioactive assays, fluorescent membrane probes and molecular dynamics simulations provide evidence of selective accumulation of gemcitabine-squalene in the plasma membranes with disrupted lipid asymmetry and its subsequent preferential uptake by malignant cells. This causes pronounced cytotoxicity on cancer cells in comparison to their benign counterparts originating from the same tissue.

Drawing on entrepreneurship education and entrepreneurial intention literature, this paper develops and tests a model that aims to explain the relationship between students' perception of learning from entrepreneurship education programs (EEP), the theory of planned behavior and entrepreneurial intention across Latin American countries.,This study uses data from the Global University Entrepreneurship Spirit Student’s Survey (GUESSS) project 2018 for 11 Latin American countries. Structural equation modeling is used to validate the theoretical model; this offers advantages over traditional multivariate techniques in evaluating measurement errors, estimation of latent variables and specification of models.,The main results suggest that a positive perception of learning from EEP is related to the antecedents of entrepreneurial intention. Moreover, attitude toward entrepreneurial behavior and perceived behavior control positively influences entrepreneurial intention across Latin American undergraduate students. The findings contribute to a better understanding of the role of EEP in terms of the antecedents of the intention and, in addition, provide evidence to the theory of planned behavior from a large sample in an emerging region.,The theory of planned behavior is one of the most important theoretical frameworks to explain entrepreneurial intention. However, in Latin American countries, quality research is hindered by the lack of data and valid measures. Therefore, the paper adds value by looking at the perception of learning from EEP and its relationship with the antecedents of intention. Likewise, it validates the dimensions of the theory of planned behavior and its relationship to entrepreneurial intention, considering a broad sample of university students in Latin America.,Con base en la literatura sobre educacion en emprendimiento e intencion emprendedora, este estudio desarrolla y prueba un modelo que busca explicar la relacion entre la percepcion de los estudiantes sobre el aprendizaje de los programas de educacion en emprendimiento, la Teoria del Comportamiento Planificado y la intencion emprendedora en los paises de America Latina.,Este estudio utiliza datos del proyecto Global University Entrepreneurship Spirit Student Survey (GUESSS) 2018 para 11 paises de America Latina. Se valida el modelo teorico mediante modelos de ecuaciones estructurales; esta tecnica ofrece ventajas sobre otras de analisis multivariante tradicionales relacionadas con la evaluacion de errores de medicion, estimacion de variables latentes y especificacion del modelo.,Los principales resultados sugieren que una percepcion positiva del aprendizaje de los programas de educacion en emprendimiento se relaciona con los antecedentes de la intencion emprendedora. Ademas, la actitud hacia el comportamiento emprendedor y el control del comportamiento percibido influyen positivamente en la intencion de emprender de los estudiantes universitarios latinoamericanos. Estos hallazgos contribuyen a una mejor comprension del rol de la educacion en emprendimiento en terminos de los antecedentes de la intencion y proporcionan evidencia de la Teoria del Comportamiento Planificado de una gran muestra en una region emergente.,la Teoria del Comportamiento Planificado es uno de los marcos teoricos mas importantes para explicar la intencion emprendedora. Sin embargo, en los paises de America Latina, la investigacion de calidad se ve obstaculizada por la falta de datos y medidas validas. Por lo tanto, el trabajo agrega valor al observar la percepcion del aprendizaje de los programas de educacion en emprendimiento y su relacion con los antecedentes de la intencion. Asimismo, validando las dimensiones de la Teoria del Comportamiento Planificado y su relacion con la intencion emprendedora, considerando una amplia muestra de estudiantes universitarios latinoamericanos.

La enfermedad de Behçet (EB) es una vasculitis mulsistémica, fue descrita como un complejo trisintomático de úlceras orales, úlceras genitales e iritis de carácter recidivante, que afecta principalmente a adultos jóvenes. Muchas de sus manifestaciones clínicas pueden ser autolimitadas. A continuación presentamos el caso clínico de un paciente femenino de 35 años con antecedentes patológicos personales de lupus eritematoso sistémico, que presentó lesiones úlceras aftosas en mucosa oral, úlceras genitales y úlceras cutáneas, además de congestión conjuntival. El objetivo de la presente publicación es aportar un caso clínico de Enfermedad Behçet con manifestaciones dermatológicas características de la enfermedad, lo cual constituye un reto diagnóstico para una patología poco frecuente. Palabras Clave: enfermedad de Behçet, vasculitis. [1]J. Calvo Catalá, A. Baixauli Rubio, C. Campos Fernández y M. I. González-Cruz Cervellera, «Enfermedad de Behçet,» Revista de la SVR Sociedad Valenciana de Reumatología, pp. 313-330, 2015. [2]L. C. Pérez, «Enfermedad de Behçet,» An. Med. Interna (Madrid), vol. 8, 2001. [3]R. Molina, A. Huerta-Rosario, C. Alva, K. Mejía, N. Mori y R. Romero, «Enfermedad de neuro-Behçet en Perú: reporte de caso y revisión de la literatura,» Revista Biomédica Revisada Por Pares, vol. 1, nº 1, p. 1, 2017. [4]. S. Ellison L y Y. Yusuf , «Patogenia del síndrome de Behçet,» UpToDate , 2020. [5]W. Castillo González, J. González-Argote y J. Hernández Estévez, «Behcet's disease,» Cuba Reumatol, Septiembre 2014. [6]F. Davatchi, S. Assaad-Khalil, K. Calamia, B. Sadeghi-Abdollahi, M. Schirmer y C. C. Zouboulis, «The International Criteria for Behçet's Disease (ICBD): A collaborative study of 27 countries on the sensitivity and specificity of the new criteria,» Journal of the European Academy of Dermatology and Venereology, pp. 338-347, 2014. [7]W. González, J. González-Argote y E. J. Hernández, « Enfermedad de Behçet Enfermedad de Behçet Behcet's disease,» Revista Cubana de Reumatología, vol. 3, pp. 309-321, 2014. [8]J. E. Acad, «The International Criteria for Behçet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria,» JEADV, pp. 338-347, 2013. [9]M. R. Carballeira y G. Espinosa Garriga , «MONOGRÁFICO: Enfermedades de Behçet,» Cuadernos de Autoinmunidad, pp. 4-6, 2011. [10]M. E. Alfonso Valdés, «Síndrome de Behcet ARTÍCULO,» Revista Cubana de Hematologia, Inmunologia y Hemoterapia, vol. 36, pp. 301-315, 2016. [11]S. D, B. Wechsler y K. Desseaux , «Mortality in Behçet's disease,» Arthritis Rheum., p. 2806–2812, 2010.

The skin is the first line of defence against most infections, including those by arthropod-borne viruses (arboviruses). The skin is a compartmentalised organ populated by a variety of immune cells that play a critical role in coordinating immune responses after skin infection. Arboviruses such as Ross River virus (RRV) and Chikungunya virus (CHIKV) cause debilitating musculoskeletal and arthritic disease and are considered significant public health threats of major global concern due to the scale of outbreaks, and the limited treatment options available. To understand the dynamics of arthritogenic arbovirus dissemination following skin infection, we developed a pathogenic model of RRV infection to mimic a mosquito bite. We found that inflammatory monocytes, neutrophils and dermal macrophages dominated the early inflammatory response in the skin. In addition, we found that RRV-infected CD11b+ migratory cells translocate to the skin draining lymph nodes. Importantly, we unveiled a critical role for viral envelope glycosylation in driving viral dissemination kinetics and disease severity. Intradermal infection with RRV derived from mosquito cells resulted in more severe disease compared to RRV derived from mammalian cells. This difference in disease was accompanied by glycosylationspecific transcriptional response in the skin after intradermal infection. Interestingly we also show evidence indicating that viral envelope glycosylation dictates the dissemination of RRV to target tissues in muscle and joint. Using a new model of cutaneous arboviral infection, we show previously unappreciated mechanisms of immune response and viral dissemination that, in future, will help develop novel approaches to limit arboviral dissemination and ameliorate disease outcomes.

The purpose of this paper is to focus on the state of entrepreneurship research in the Latin American context, with special emphasis on international entrepreneurship research developed in this region. Therefore, the aim and contribution are to identify the main themes in the literature about entrepreneurship and show the evolution of entrepreneurship research in Latin America to stimulate the research and provide future research lines.,The methodology is based in a systematic literature review, using 128 articles published between 2002 and 2018, in scientific journals in the region according to SCImago Journal & Country Rank.,The results show the evolution through the journals, authors, topics and methodologies used by the researchers. It is emphasized that there is a very low level of research in international entrepreneurship in Latin America. This result is coherent with higher levels of entrepreneurship in Latin American countries but very few oriented to international markets. This is one of the challenges considering the importance of this field.,Entrepreneurship is a field of study that has grown throughout history. Even so, in the Latin American context, research published in high impact journals is limited. This paper is the first systematic literature review and thematic analysis of research on the field of entrepreneurship in the Latin American context. In this way, it serves as encouragement for future research, providing possibilities and challenges within the field of study.,Este articulo presenta el estado de la investigacion en emprendimiento en el contexto latinoamericano, haciendo enfasis en el emprendimiento internacional.,Se llevo a cabo una revision sistematica de la literatura en la cual se encontraron 147 articulos, publicados entre 2002 y 2018 en revistas cientificas de la region de acuerdo con el ranking SCImago Journal & Country Rank (SJR).,Los hallazgos presentan la evolucion de las revistas, los autores, los temas y las metodologias usadas por los investigadores. Se resalta el bajo nivel de investigaciones en emprendimiento internacional en la region, lo cual es coherente con altas tasas de actividad emprendedora de Latinoamerica, pero baja orientacion a la internacionalizacion. Este es uno de los retos de los paises, considerando la importancia de esta area.,Aunque la investigacion en emprendimiento ha aumentado a traves de la historia, en el contexto latinoamericano las publicaciones en revistas de alto impacto son limitadas. Este estudio es la primera revision sistematica de la literatura y analisis tematico de la investigacion en emprendimiento. En este sentido, los resultados sirven somo estimulo a la investigacion futura mostrando las oportunidades y los desafios dentro de este campo de estudio.

Humans use simple probing actions to develop intuition about the physical behaviour of common objects. Such intuition is particularly useful for adaptive estimation of favourable manipulation strategies of those objects in novel contexts. For example, observing the effect of tilt on a transparent bottle containing an unknown liquid provides clues on how the liquid might be poured. It is desirable to equip general-purpose robotic systems with this capability because it is inevitable that they will encounter novel objects and scenarios. In this paper, we teach a robot to use a simple, specified probing strategy – stirring with a stick – to reduce spillage while pouring unknown liquids. In the probing step, we continuously observe the effects of a real robot stirring a liquid, while simultaneously tuning the parameters to a model (simulator) until the two outputs are in agreement. We obtain optimal simulation parameters, characterising the unknown liquid, via a Bayesian Optimiser that minimises the discrepancy between real and simulated outcomes. Then, we optimise the pouring policy conditioning on the optimal simulation parameters determined via stirring. We show that using stirring as a probing strategy results in reduced spillage for three qualitatively different liquids when executed on a UR10 Robot, compared to probing via pouring. Finally, we provide quantitative insights into the reason for stirring being a suitable calibration task for pouring – a step towards automatic discovery of probing strategies.

free open access article 31 p.; International audience; In this work, we have explored natural unmodified low- and high-density lipoproteins (LDL and HDL) as selective delivery vectors in colorectal cancer therapy. We show in vitro in cultured cells and in vivo (NanoSPECT/CT) in the CT-26 mice colorectal cancer model that LDLs are mainly taken up by cancer cells, while HDLs are preferentially taken up by macrophages. We loaded LDLs with cisplatin and HDLs with the heat shock protein-70 inhibitor AC1LINNC, turning them into a pair of “Trojan horses” delivering drugs selectively to their target cells as demonstrated in vitro in human colorectal cancer cells and macrophages, and in vivo. Coupling of the drugs to lipoproteins and stability was assessed by mass and raman spectrometry analysis. Cisplatin vectorized in LDLs led to better tumor growth suppression with strongly reduced adverse effects such as a renal or liver toxicity. AC1LINNC vectorized into HDLs induced a strong oxidative burst in macrophages and innate anti-cancer immune response. Cumulative anti-tumor effect was observed for both drug-loaded lipoproteins. Altogether, our data show that lipoproteins from patient’s blood can be used as natural nanocarriers allowing cell specific targeting, paving the way toward more efficient, safer and personalized use of chemo-and immunotherapeutic drugs in cancer

At labor, the myometrium is infiltrated by a massive influx of macrophages that secrete high levels of pro-inflammatory cytokines inducing the expression of specific labor-associated markers. However, the interactions between myocytes and macrophages and the role of macrophages in the myometrium at labor remain to be elucidated. In this work, we studied the role of myometrium-infiltrated macrophages and their interaction with myocytes in lipopolysaccharide-induced preterm labor. A co-culture model of human primary myometrial cells and macrophages was developed and validated. Collagen lattices were used to evaluate myocyte contraction. Differentiation steps were assessed by (i) phalloidin and vinculin staining for cytoskeleton reorganization, (ii) gap junction protein alpha 1 expression and scrape loading/dye transfer with Lucifer Yellow for gap junction intercellular communication, and (iii) calcium imaging for cell excitability. We demonstrated that macrophages favored lipopolysaccharide-induced contraction and early differentiation of myometrial cells. Transwell assays showed that previous activation of macrophages by lipopolysaccharide was essential for this differentiation and that macrophage/myocyte interactions involved macrophage release of reactive oxygen species (ROS). The effects of macrophage-released ROS in myometrial cell transactivation were mimicked by H2O2, suggesting that superoxide anion is a major intermediate messenger in macrophage/myocyte crosstalk during labor. These novel findings provide the foundation for innovative approaches to managing preterm labor, specifically the use of antioxidants to inhibit the initial stages of labor before the contractile phenotype has been acquired. In addition, the co-culture model developed by our team could be used in future research to decipher pathophysiological signaling pathways or screen/develop new tocolytics.

International audience; BACKGROUND: We previously showed that supernatants of Lactobacillus biofilms induced an anti-inflammatory response by affecting the secretion of macrophage-derived cytokines, which was abrogated upon immunodepletion of the stress protein GroEL. METHODS: We purified GroEL from L. reuteri and analysed its anti-inflammatory properties in vitro in human macrophages isolated from buffy coats, ex vivo in explants from human biopsies and in vivo in a mouse model of DSS induced intestinal inflammation. As a control, we used GroEL purified (LPS-free) from E. coli. RESULTS: We found that L. reuteri GroEL (but not E. coli GroEL) inhibited pro-inflammatory M1-like macrophages markers, and favored M2-like markers. Consequently, L. reuteri GroEL inhibited pro-inflammatory cytokines (TNFα, IL-1β, IFNγ) while favouring an anti-inflammatory secretome. In colon tissues from human biopsies, L. reuteri GroEL was also able to decrease markers of inflammation and apoptosis (caspase 3) induced by LPS. In mice, we found that rectal administration of L. reuteri GroEL (but not E. coli GroEL) inhibited all signs of haemorrhagic colitis induced by DSS including intestinal mucosa degradation, rectal bleeding and weight loss. It also decreased intestinal production of inflammatory cytokines (such as IFNγ) while increasing anti-inflammatory IL-10 and IL-13. These effects were suppressed when animals were immunodepleted in macrophages. From a mechanistic point of view, the effect of L. reuteri GroEL seemed to involve TLR4, since it was lost in TRL4(-/-) mice, and the activation of a non-canonical TLR4 pathway. CONCLUSIONS: L. reuteri GroEL, by affecting macrophage inflammatory features, deserves to be explored as an alternative to probiotics.

International audience; Main conclusionThe involvement of a WRKY transcription factor in the regulation of lignan biosynthesis in flax using a hairy root system is described.AbstractSecoisolariciresinol is the main flax lignan synthesized by action of LuPLR1 (pinoresinol-lariciresinol reductase 1). LuPLR1 gene promoter deletion experiments have revealed a promoter region containing W boxes potentially responsible for the response to Fusarium oxysporum. W boxes are bound by WRKY transcription factors that play a role in the response to stress. A candidate WRKY transcription factor, LuWRKY36, was isolated from both abscisic acid and Fusarium elicitor-treated flax cell cDNA libraries. This transcription factors contains two WRKY DNA-binding domains and is a homolog of AtWRKY33. Different approaches confirmed LuWRKY36 binding to a W box located in the LuPLR1 promoter occurring through a unique direct interaction mediated by its N-terminal WRKY domain. Our results propose that the positive regulator action of LuWRKY36 on the LuPLR1 gene regulation and lignan biosynthesis in response to biotic stress is positively mediated by abscisic acid and inhibited by ethylene. Additionally, we demonstrate a differential Fusarium elicitor response in susceptible and resistant flax cultivars, seen as a faster and stronger LuPLR1 gene expression response accompanied with higher secoisolariciresinol accumulation in HR of the resistant cultivar.

International audience; The LuPLR1 gene encodes a pinoresinol lariciresinol reductase responsible for the biosynthesis of (+)-secoisolariciresinol, a cancer chemopreventive lignan, highly accumulated in the seedcoat of flax (Linum usitatissimum L.). Abscisic acid (ABA) plays a key role in the regulation of LuPLR1 gene expression and lignan accumulation in both seeds and cell suspensions, which require two cis-acting elements (ABRE and MYB2) for this regulation. Ca2+ is a universal secondary messenger involved in a wide range of physiological processes including ABA signaling. Therefore, Ca2+ may be involved as a mediator of LuPLR1 gene expression and lignan biosynthesis regulation exerted by ABA. To test the potential implication of Ca2+ signaling, a pharmacological approach was conducted using both flax cell suspensions and maturing seed systems coupled with a ß-glucuronidase reporter gene experiment, RT-qPCR analysis, lignan quantification as well as Ca2+ fluorescence imaging. Exogenous ABA application results in an increase in the intracellular Ca2+ cytosolic concentration, originating mainly from the extracellular medium. Promoter-reporter deletion experiments suggest that the ABRE and MYB2 cis-acting elements of the LuPLR1 gene promoter functioned as Ca2+-sensitive sequences involved in the ABA-mediated regulation. The use of specific inhibitors pointed the crucial roles of the Ca2+ sensors calmodulin-like proteins and Ca2+-dependent protein kinases in this regulation. This regulation appeared conserved in the two different studied systems, i.e. cell suspensions and maturing seeds. A calmodulin-like, LuCML15b, identified from gene network analysis is proposed as a key player involved in this signal transduction since RNAi experiments provided direct evidences of this role. Taken together, these results provide new information on the regulation of plant defense and human health-promoting compounds, which could be used to optimize their production.

The LuPLR1 gene encodes a pinoresinol lariciresinol reductase responsible for the biosynthesis of (+)-secoisolariciresinol, a cancer chemopreventive lignan, highly accumulated in the seedcoat of flax (Linum usitatissimum L.). Abscisic acid (ABA) plays a key role in the regulation of LuPLR1 gene expression and lignan accumulation in both seeds and cell suspensions, which require two cis-acting elements (ABRE and MYB2) for this regulation. Ca

International audience; HSF1 is a transcription factor that plays a key role in circadian resetting by temperature. We have used zebrafish embryos to decipher the roles of zHsf1, heat and light on zper2 transcription in vivo. Our results show that heat shock (HS) stimulated zper2 expression in the dark but has no cumulative effect combined with light. After light exposition, zper2 expression was 2.7 fold increased threefold in the hsf1-morphants in comparison to control embryos. Our results show that zHsf1 plays a positive role in HS-driven expression of zper2 in the dark but seems to act as an attenuator in the presence light.

Podophyllotoxin is a naturally occurring plant lignan with potent anticancer applications. Its supply from Podophyllum hexandrum , its current natural source, is becoming ever scarcer and alternative sources are required. Deoxypodophyllotoxin, one precursor of podophyllotoxin, could be an interesting commercial alternative. In such a context, Callitris species could represent an attractive source of this compound. However, to date, only two Callitris species have been analyzed for their content in lignans. In this work, we were able to detect high amounts of deoxypodophyllotoxin in leaves of C. endlicheri , C. rhomboidea , C. preissii and C. drummondii . The highest content (5.8 mg/g DW) was measured in young leaves of C. endlicheri . Moreover, important variation was observed among the four species and the different tested organs but no significant variation over the two different years studied. Regarding our results, aerial parts of Callitris species should be considered as a promising raw source for the large scale production of deoxypodophyllotoxin.

This study provides new insights into the biosynthesis regulation and in planta function of the lignan yatein in flax leaves. Pinoresinol–lariciresinol reductases (PLR) catalyze the conversion of pinoresinol into secoisolariciresinol (SECO) in lignan biosynthesis. Several lignans are accumulated in high concentrations, such as SECO accumulated as secoisolariciresinol diglucoside (SDG) in seeds and yatein in aerial parts, in the flax plant (Linum usitatissimum L.) from which two PLR enzymes of opposite enantioselectivity have been isolated. While LuPLR1 catalyzes the biosynthesis of (+)-SECO leading to (+)-SDG in seeds, the role(s) of the second PLR (LuPLR2) is not completely elucidated. This study provides new insights into the in planta regulation and function of the lignan yatein in flax leaves: its biosynthesis relies on a different PLR with opposite stereospecificity but also on a distinct expression regulation. RNAi technology provided evidence for the in vivo involvement of the LuPLR2 gene in the biosynthesis of (−)-yatein accumulated in flax leaves. LuPLR2 expression in different tissues and in response to stress was studied by RT-qPCR and promoter-reporter transgenesis showing that the spatio-temporal expression of the LuPLR2 gene in leaves perfectly matches the (−)-yatein accumulation and that LuPLR2 expression and yatein production are increased by methyl jasmonate and wounding. A promoter deletion approach yielded putative regulatory elements. This expression pattern in relation to a possible role for this lignan in flax defense is discussed.

This study analysed the influence of university education factors on the entrepreneurial intentions of 35,335 Latin American students, using structural equation modelling. The main contribution of this study is a model of higher education factors as antecedents in the theory of planned behaviour, to explain the entrepreneurial intention in developing countries. The main results show that entrepreneurship courses and the favourable perception of an entrepreneurial university environment were positively related to entrepreneurial intentions. Although both variables have a direct effect on such intentions, the university environment was a stronger one. These results deepen the extant empirical research on the subject, since most scholars have focused on indirect effects instead. Universities should design strategies beyond their classrooms that are aimed at improving the intentions that will guide students' entrepreneurial behaviour and choices.