Angular analysis of B0→D∗−D∗+s with D∗+s→D+sγ decays

The first full angular analysis of the B0→D∗−D∗+s decay is performed using 6 fb−1 of pp collision data collected with the LHCb experiment at a centre-of-mass energy of 13 TeV. The D∗+s→D+sγ and D*− → D¯¯¯¯0π− vector meson decays are used with the subsequent D+s → K+K−π+ and D¯¯¯¯0 → K+π− decays. All helicity amplitudes and phases are measured, and the longitudinal polarisation fraction is determined to be fL = 0.578 ± 0.010 ± 0.011 with world-best precision, where the first uncertainty is statistical and the second is systematic. The pattern of helicity amplitude magnitudes is found to align with expectations from quark-helicity conservation in B decays. The ratio of branching fractions [ℬ(B0→D∗−D∗+s) × ℬ(D∗+s→D+sγ)]/ℬ(B0 → D*−D+s) is measured to be 2.045 ± 0.022 ± 0.071 with world-best precision. In addition, the first observation of the Cabibbo-suppressed Bs → D*−D+s decay is made with a significance of seven standard deviations. The branching fraction ratio ℬ(Bs → D*−D+s)/ℬ(B0 → D*−D+s) is measured to be 0.049 ± 0.006 ± 0.003 ± 0.002, where the third uncertainty is due to limited knowledge of the ratio of fragmentation fractionsS

Recomendaciones para la práctica de ejercicio físico en pacientes cardiópatas en edad escolar

As cardiopatías conxénitas constitúen o defecto conxénito máis frecuente, e nas últimas décadas asistimos a un importante avance no tratamento das mesmas. Este documento consiste nunha recompilación de recomendacións para a práctica da actividade física, no ámbito escolar galego, para os nenos/as entre 6 e 16 anos, portadores da maioría das cardiopatías conxénitas e familiares.Las cardiopatías congénitas constituyen el defecto congénito más frecuente, y en las últimas décadas asistimos a un importante avance en el tratamiento de las mismas. Este documento consiste en una recopilación de recomendacións para la práctica de la actividade física, en el ámbito escolar gallego, para los niños y niñas entre 6 y 16 años, portadores de la mayoría de las cardiopatías congénitas y familiares

Santos Ovejero del Agua. Catedrático de la Facultad de Veterinaria y su relación con la de Biología de León

Santos Ovejero del Agua fue un personaje de una personalidad extraordinaria, sin cuya presencia sería difícil de entender la vida social, académica, universitaria y empresarial de la ciudad y provincia de León desde el final de la guerra civil hasta el final de los años 60. Nacido, criado y fallecido en León (1906-1983), suma un espíritu inquieto, bien formado, gran personalidad, de perfil internacional, que ostentó responsabilidades importantes en la vida pública universitaria de la ciudad y fue catedrático y decano de la Facultad de Veterinaria, un visionario de sus posibilidades de proyección social, que proporcionó las primeras claves para la ampliación de estudios universitarios en lo que después sería Facultad de Biología y pionero en la actividad industrial biotecnológica de la Sanidad Animal

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Species Distribution Models applied to exotic invasive management and to conservation of threatened species

88 p.[ES] En el Antropoceno, explorar soluciones para la conservación de las plantas, el sustento de la vida en la tierra, frente a riesgos globales como las invasiones biológicas, debe ser una prioridad. La demanda creciente de nuevos enfoques de modelización de aplicación en gestión, conservación y evaluación de riesgos sobre la biodiversidad, se incrementó en los últimos años. La ciencia de la modelización debe avanzar en esta dirección, proporcionando recomendaciones que permitan responder a diferentes casuísticas, basadas en experiencias reales. El objetivo de esta Tesis es resolver preguntas importantes acerca de esta cuestión, utilizando enfoques de trabajo complementarios, que puedan extrapolarse a otras situaciones equivalentes. Como especies modelo estudiamos Paraserianthes lophantha (Fabaceae), una especie exótica invasora, pariente cercana de las acacias australianas, Acacia spp. y Quercus lusitanica (Fagaceae), especie amenazada y de interés para la conservación. En concreto, evaluamos el riesgo del potencial invasor de P. lophantha sobre Q. lusitanica de forma holística, utilizando como herramientas los modelos de distribución de especies, complementados con estudios experimentales de respuesta de las plántulas de ambas especies a la sequía, fase crítica del desarrollo. Los análisis se realizaron con registros de presencia localizados a partir de citas confiables confirmadas de las especies incluidas en bases de datos de referencia de plantas. Además, todos los registros de Galicia, se consultaron en su fuente original y se localizaron en campo para georreferenciar con precisión. Las variables ambientales utilizadas proceden de bases de datos relacionadas con el clima (WORLDCLIM, Atlas Climático de la Península Ibérica y CHELSA), usos del suelo (SIOSE), topografía o edafología. En algunos casos se generaron utilizando sistemas de información geográfica (ArcGis y Qgis). Exploramos (1) diferentes enfoques de modelización de la distribución de especies (SDMs) aplicables a la gestión de áreas pequeñas, analizando el potencial predictivo de modelos calibrados en diferentes escalas para dirigir las labores de gestión en áreas muy reducidas; (2) el potencial de los SDMs de especies exóticas, calibrados con datos de los rangos invadidos, comparando el potencial predictivo de SDMs de Paraserianthes lophantha calibrados con datos del rango nativo versus datos del rango invadido -comparando a su vez las predicciones de modelos calibrados a escala regional versus escala local; (3) introducimos en la modelización variables relacionadas con las posibles vías de introducción y dispersión de especies exóticas -datos de la cobertura del suelo; (4) evaluamos la posible interacción competitiva en condiciones de sequía de P. lophantha frente a Quercus lusitanica; (5) estudiamos la dinámica de nicho de P. lophantha entre varios rangos invadidos, para la elección de las áreas de calibración de los modelos predictivos así como para una mejor comprensión de las tolerancias de la especie; (6) evaluamos si el estudio multisitio de la dinámica de nicho entre el área de distribución nativa y más de un área de invasión puede contribuir a anticipar el potencial de expansión de las especies exóticas invasoras; (7) evaluamos si los resultados de un análisis de solapamiento de nicho a pequeña escala pueden ser utilizados para fines de conservación local; (8) proyectamos las distribuciones de P. lophantha y Q. lusitanica en escenarios climáticos futuros; (9) evaluamos la posible amenaza de P. lophantha sobre Q. lusitanica, obteniendo mapas de riesgo, combinando diferentes SDMs generados para ambas; (10) implementamos los resultados en el análisis de riesgos de P. lophantha a nivel europeo. El cálculo de modelos de distribución (SDMs) más precisos (calibrados con datos subóptimos), pero con variables de grano fino (25m) significativas, que expliquen su distribución en esas localidades (ej usos del suelo, orientación…) y la selección de la complejidad del modelo óptima, utilizando una evaluación cualitativa de los mismos, permitió una discriminación del espacio más adecuada para Paraserianthes lophantha y Quercus lusitanica que los SDMs calibrados con datos de los rangos de distribución completos, calibrados con variables de grano grueso (1Km) climáticas, lo que refuerza la utilidad de combinar enfoques locales y regionales para promover acciones de gestión local. Además, los SDMs de P. lophantha, calibrados en su rango invadido, fueron más útiles que los SDMs calibrados en su rango nativo, lo que demuestra que su uso como apoyo a la gestión debe aplicarse al menos con fines exploratorios. Esto permite incorporar variables significativas para la distribución de especies exóticas a pequeña escala -por ejemplo, los usos del suelo- o predecir la distribución de especies exóticas de las que se sospecha que han experimentado cambios en su nicho. Así mismo, encontramos que los SDMs calibrados a escala regional, utilizando variables de alta resolución, de enfoque local, son adecuados para mejorar las predicciones en áreas locales, al incluir información sobre un mayor número de datos de presencia y reducir el sobreajuste a los datos locales. Además, proporcionan una discriminación nítida de las zonas en las que deben centrarse las acciones de conservación a escala regional. Todos estos enfoques permitieron superar las limitaciones de evaluar y gestionar el riesgo local de una invasión biológica sobre una población disyunta. Nuestro estudio experimental no identificó, que ninguna de las especies superará competitivamente a la otra en las condiciones y etapa del desarrollo estudiadas. El efecto del estrés hídrico fue mayor en Q. lusitanica, que experimentó una gran reducción en sus potenciales hídricos y mortalidad al someterla al tratamiento de sequía. La exploración de la dinámica de nicho de P. lophantha mediante comparaciones multisitio, considerando diferentes áreas de invasión, mejoró la comprensión de la invasión, evitó infravalorar el potencial de expansión de P. lophantha a gran escala en Europa y probar que, utilizar datos tanto del rango nativo como del invadido es más adecuado para predecir el potencial de expansión de la especie. También, estudiamos el solapamiento de su nicho con el de la población de Quercus lusitanica a pequeña escala en Monte Pindo (A Coruña, Galicia, España), demostrando que P. lophantha es una colonizadora exitosa que puede amenazar seriamente este espacio natural. Este análisis también reforzó los resultados de los estudios predictivos anteriores que señalan que la gestión local para evitar la expansión de P. lophantha debe ser una preocupación para la conservación de Q. lusitanica. Los modelos predictivos de distribución de ambas especies a gran escala (Europa) permitieron corroborar que Paraserianthes lophantha tiene un notable potencial de expansión sobre las zonas costeras europeas de clima suave. Sin embargo, se espera que la expansión en los climas de la fachada Atlántica sea más conflictiva que en las costas del mar Mediterráneo. Respecto a Quercus lusitanica, prevemos que los efectos del cambio climático serán mucho más importantes y podrían comprometer seriamente la conservación de la especie. La combinación de los SDMs calibrados con los diferentes enfoques en esta tesis (escala regional y local) en modelos de riesgo, corroboraron la hipótesis de que P. lophantha podría suponer una amenaza para la conservación de Q. lusitanica al identificar las áreas con alto riesgo de invasión, en las que se podría producir el contacto entre ambas especies. Finalmente se realizó el análisis de riesgo siguiendo el análisis europeo para P. lophantha, aprovechando los resultados de los capítulos anteriores. Los trabajos de modelización de la distribución de especies permitieron aportar nueva información para responder a las cuestiones del modelo, aportando evidencias científicas relativas a la capacidad de establecimiento y expansión e impacto de la especie en el territorio europeo, incorporando también aspectos del cambio climático.[EN] In the Anthropocene, exploring solutions for the conservation of plants, the support of life on earth, in the face of global risks such as biological invasion, must be a priority. The growing demand for new modeling approaches for application in biodiversity management, conservation and risk assessment has increased in recent years. The science of modeling must advance in this direction, providing recommendations that can respond to different cases, based on real experience. The aim of this Thesis is to resolve important questions about this issue, using complementary approaches that can be extrapolated to other equivalent situations. As model species we studied Paraserianthes lophantha (Fabaceae), an invasive alien species, a close relative of the Australian acacias, Acacia spp. and Quercus lusitanica (Fagaceae), a threatened species of conservation concern. Specifically, we assessed the risk of the invasive potential of P. lophantha on Q. lusitanica holistically, using species distribution models as tools, complemented with experimental studies of the response of the seedlings of both species to drought, a critical stage in the plants development. The models were fitted with localized occurrence records from reliable confirmed citations of the species included in reference plant databases. In addition, all the records from Galicia were consulted in their original source, and located in the field for them to be more accurately georeferenced. The environmental variables come from databases related to climate (WORLDCLIM, Climatic Atlas of the Iberian Peninsula and CHELSA), land use (SIOSE), topography, pedology or hydrography. In some cases they were obtained using geographic information systems (ArcGis and Qgis). We explored (1) different species distribution modeling approaches (SDMs) applicable to small-area management, analyzing the predictive potential of models calibrated at different scales to direct management efforts in very small areas; (2) the potential of exotic species SDMs, calibrated with data from invaded ranges, comparing the predictive potential of SDMs of P. lophantha calibrated with native versus invaded range data - comparing in turn the predictions of models calibrated at regional versus local scales; (3) we introduce into the modeling variables related to the possible pathways of introduction and dispersal of exotic species - land cover data; (4) we evaluate the possible competitive interaction under drought conditions of P. lophantha versus Quercus lusitanica; (5) we study the niche dynamics of P. lophantha among various invaded ranges, for the choice of calibration areas for predictive models as well as for a better understanding of the species’ tolerance; (6) we evaluated whether the multisite study of niche dynamics between the native range and more than one invasion area can contribute to anticipate the expansion potential of invasive alien species; (7) we evaluate whether the results of a small-scale niche overlap analysis can be used for local conservation purposes; (8) we project the distributions of P. lophantha and Q. lusitanica in future climate scenarios; (9) we assessed the potential threat of P. lophantha on Q. lusitanica, obtaining risk maps, combining different SDMs generated for both; (10) we implemented the results in the risk analysis of P. lophantha at the European level. The most accurate species distribution models (SDMs), calibrated with suboptimal data, but with significant fine-grained variables (25m), which explain the distribution in those localities (e.g. land use, orientation...), and the selection of optimal model complexity, using a qualitative evaluation, allowed a more adequate spatial discrimination for Paraserianthes lophantha and Quercus lusitanica than the SDMs. The selection of the optimal model complexity, using a qualitative assessment, allowed a more adequate spatial discrimination for P. lophantha and Q. lusitanica than SDMs calibrated with full range data, calibrated with coarse-grained (1km) climatic variables, which reinforces the usefulness of combining local and regional approaches to promote local management actions. Furthermore, SDMs of P. lophantha, calibrated in its invaded range, were more useful than SDMs calibrated in its native range, demonstrating that their use to support management should be applied at least for exploratory purposes. This allows incorporating significant variables for the distribution of exotic species at small scales-for example, land uses-or predicting the distribution of exotic species suspected to have undergone niche changes. Likewise, we find that regionally calibrated SDMs, using high-resolution, locally focused variables, are suitable for improving predictions in local areas by including information on a larger number of occurrence data and reducing overfitting to local data. In addition, they provide a sharp discrimination of areas where conservation actions should be focused at a regional scale. All of these approaches overcame the limitations of assessing and managing the local risk of a biological invasion on a disjunct population. Our experimental study did not identify that either species would competitively outcompete the other under these conditions and stage of development. The effect of water stress was greater on Q. lusitanica, which experienced a large reduction in water potential and mortality when subjected to the drought treatment. Exploring the niche dynamics of P. lophantha through multi-site comparisons, considering different areas of invasion, improved the understanding of the invasion, avoided underestimating the potential for large- scale expansion of P. lophantha in Europe, and proved that using data from both native and invaded ranges is more adequate to predict the expansion potential of the species. Also, we studied the overlap of its niche with that of the small-scale Q. lusitanica population in Monte Pindo (A Coruña, Galicia, Spain), demonstrating that P. lophantha is a successful colonizer that can seriously threaten this natural area. This analysis also reinforced the results of previous predictive studies indicating that local management to prevent the expansion of P. lophantha should be a concern for the conservation of Q. lusitanica. Ensemble prediction models of the distribution of the two species on a large scale (Europe) corroborated that Paraserianthes lophantha has a remarkable potential for expansion over European coastal areas with a mild climate. However, the expansion in the climates of the Atlantic façade is expected to be more conflicting than on the coasts of the Mediterranean Sea. Regarding Quercus lusitanica, we anticipate that the effects of climate change will be much more important and could seriously compromise the conservation of the species. The combination of the SDMs calibrated with the different approaches in this thesis (regional and local scale) in risk models, corroborated the hypothesis that P. lophantha could pose a threat to the conservation of Q. lusitanica by identifying areas with a high risk of invasion, in which contact between both species could occur. Finally, the risk analysis was performed following the European analysis for Paraserianthes lophantha, using the results from the previous chapters. The species distribution modeling work provided new information to answer the questions of the model, providing scientific evidence regarding the species’ establishment and expansion capacity and impact the European territory, also incorporating aspects of climate change

Unravelling the ecological drivers of <i>Schistostega pennata</i> (Hedw.) F.Weber & D.Mohr on the Iberian Peninsula: distribution and conservation

In the Iberian Peninsula, Schistostega pennata is a rare, acidophilic, Holarctic moss with a characteristic glowing protonema when illuminated by sunlight. It is typically found in dark and humid habitats and is categorised as Threatened or Near Threatened on the Iberian Red Lists. The main aim of this study was to improve knowledge of the distribution, ecology and conservation of S. pennata on the Iberian Peninsula. All data that were available to us for Schistostega pennata on the Iberian Peninsula (relating to distribution, ecology, phenology) were compiled from the literature, citizen science platforms, and our own observations. Species distribution models were created in Maxent to provide the first approximation to its potential Iberian distribution. Twenty-six new populations of Schistostega pennata were located, making a total of 73 records for the Iberian Peninsula, mostly from natural and artificial caves, cavities, mines and crevices, and essentially on siliceous substrates. All observations corresponded to areas with abundant rainfall, mild temperatures, and at least some oceanic influence. Species distribution models predicted an expanded potential climatic range in the Iberian temperate region and several montane Mediterranean areas. There remains very little information on Schistostega pennata on the Iberian Peninsula. Existing data coincide with the ecology of the species, although other niches are exploited in other parts of the world that do not seem to occur in this area. It is important to promote its conservation, given the fragmentation of its populations and habitat requirements. Monitoring and initiation of exhaustive sampling campaigns involving citizen science could be a good way to approach this.</p

CRISPR/dCAS9-mediated DNA demethylation screen identifies functional epigenetic determinants of colorectal cancer

Abstract Background Promoter hypermethylation of tumour suppressor genes is frequently observed during the malignant transformation of colorectal cancer (CRC). However, whether this epigenetic mechanism is functional in cancer or is a mere consequence of the carcinogenic process remains to be elucidated. Results In this work, we performed an integrative multi-omic approach to identify gene candidates with strong correlations between DNA methylation and gene expression in human CRC samples and a set of 8 colon cancer cell lines. As a proof of concept, we combined recent CRISPR-Cas9 epigenome editing tools (dCas9-TET1, dCas9-TET-IM) with a customized arrayed gRNA library to modulate the DNA methylation status of 56 promoters previously linked with strong epigenetic repression in CRC, and we monitored the potential functional consequences of this DNA methylation loss by means of a high-content cell proliferation screen. Overall, the epigenetic modulation of most of these DNA methylated regions had a mild impact on the reactivation of gene expression and on the viability of cancer cells. Interestingly, we found that epigenetic reactivation of RSPO2 in the tumour context was associated with a significant impairment in cell proliferation in p53−/− cancer cell lines, and further validation with human samples demonstrated that the epigenetic silencing of RSPO2 is a mid-late event in the adenoma to carcinoma sequence. Conclusions These results highlight the potential role of DNA methylation as a driver mechanism of CRC and paves the way for the identification of novel therapeutic windows based on the epigenetic reactivation of certain tumour suppressor genes

Search for Bc+→π+μ+μ−B_c^+\to\pi^+\mu^+\mu^- decays and measurement of the branching fraction ratio B(Bc+→ψ(2S)π+)/B(Bc+→J/ψπ+){\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)

International audienceThe first search for nonresonant $B_c^+\to\pi^+\mu^+\mu^-$ decays is reported. The analysis uses proton-proton collision data collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 fb$^{-1}$. No evidence for an excess of signal events over background is observed and an upper limit is set on the branching fraction ratio ${\cal B}(B_c^+\to\pi^+\mu^+\mu^-)/{\cal B}(B_c^+\to J/\psi \pi^+) < 2.1\times 10^{-4}$ at $90\%$ confidence level. Additionally, an updated measurement of the ratio of the $B_c^+\to\psi(2S)\pi^+$ and $B_c^+\to J/\psi \pi^+$ branching fractions is reported. The ratio ${\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)$ is measured to be $0.254\pm 0.018 \pm 0.003 \pm 0.005$, where the first uncertainty is statistical, the second systematic, and the third is due to the uncertainties on the branching fractions of the leptonic $J/\psi$ and $\psi(2S)$ decays. This measurement is the most precise to date and is consistent with previous LHCb results

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5 < y_{c.m.} < 3.5$ (forward rapidity) and $-4.0 < y_{c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5 < p_{T}<10~{\rm GeV}$ and $3 < p_{T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation

Search for Bc+→π+μ+μ−B_c^+\to\pi^+\mu^+\mu^- decays and measurement of the branching fraction ratio B(Bc+→ψ(2S)π+)/B(Bc+→J/ψπ+){\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)

International audienceThe first search for nonresonant $B_c^+\to\pi^+\mu^+\mu^-$ decays is reported. The analysis uses proton-proton collision data collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 fb$^{-1}$. No evidence for an excess of signal events over background is observed and an upper limit is set on the branching fraction ratio ${\cal B}(B_c^+\to\pi^+\mu^+\mu^-)/{\cal B}(B_c^+\to J/\psi \pi^+) < 2.1\times 10^{-4}$ at $90\%$ confidence level. Additionally, an updated measurement of the ratio of the $B_c^+\to\psi(2S)\pi^+$ and $B_c^+\to J/\psi \pi^+$ branching fractions is reported. The ratio ${\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)$ is measured to be $0.254\pm 0.018 \pm 0.003 \pm 0.005$, where the first uncertainty is statistical, the second systematic, and the third is due to the uncertainties on the branching fractions of the leptonic $J/\psi$ and $\psi(2S)$ decays. This measurement is the most precise to date and is consistent with previous LHCb results