Bacterioplankton Community Composition Along Environmental Gradients in Lakes From Byers Peninsula (Maritime Antarctica) as Determined by Next-Generation Sequencing

This study comprises the first attempt to describe the planktonic bacterial communities of lakes from Byers Peninsula, one of the most significant limnological districts in the Maritime Antarctica, leveraging next-generation sequencing (NGS) technologies. For the survey, we selected 7 lakes covering the environmental gradient from inland to coastal lakes, some of them sampled both in surface and deep waters. Analysis provided just over 85,000 high quality sequences that were clustered into 864 unique Zero-radius Operational Taxonomic Units (ZOTUs) (i.e., 100% sequence similarity). Yet, several taxonomic uncertainties remained in the analysis likely suggesting the occurrence of local bacterial adaptations. The survey showed the dominance of the phyla Proteobacteria and Bacteroidetes. Among the former, the Gammaproteobacteria class, more specifically the order Betaproteobacteriales, was the dominant group, which seems to be a common trend in nutrient-limited Antarctic lakes. Most of the families and genera ubiquitously detected belonging to this class are indeed typical from ultra-oligotrophic environments, and commonly described as diazotrophs. On the other hand, among the members of the phylum Bacteroidetes, genera such as Flavobacterium were abundant in some of the shallowest lakes, thus demonstrating that also benthic and sediment-associated bacteria contributed to water bacterial assemblages. Ordination analyses sorted bacterial assemblages mainly based on the environmental gradients of nutrient availability and conductivity i.e., salinity. However, transient bacterial associations, that included the groups Clostridiaceae and Chloroflexi, also occurred as being forced by other drivers such as the influence of the nearby fauna and by the airborne microorganisms. As we intended, our NGS-based approach has provided a much greater resolution compared to the previous studies conducted in the area and confirmed to a large extent the previously obtained patterns, thus reinforcing the view of Byers as a hotspot of microbial biodiversity within Antarctica. This high microbial diversity allows the use of these aquatic ecosystems and their bacterial assemblages as sentinels for the monitoring of adaptive responses to climate change in this rapidly warming area

Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study

Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4–7 cycles, and/or every 2 months maintenance monotherapy for FL for 6–12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade ≥3 in 38 6% and were serious in 30 0%. AARs occurred in 48 6%, mostly (84 9%) at the injection site, with only 2 1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69 6%. After a median follow-up of 33 5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life

Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution

Aging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes. Deciphering the molecular basis of ventricular aging, especially by BA, could lead to major progresses in cardiac research. We aim to describe the transcriptome dynamics of the aging left ventricle (LV) in humans according to both CA and BA and characterize the contribution of microRNAs, key transcriptional regulators. BA is measured using two CA-associated transcriptional markers: CDKN2A expression, a cell senescence marker, and apparent age (AppAge), a highly complex transcriptional index. Bioinformatics analysis of 132 LV samples shows that CDKN2A expression and AppAge represent transcriptomic changes better than CA. Both BA markers are biologically validated in relation to an aging phenotype associated with heart dysfunction, the amount of cardiac fibrosis. BA-based analyses uncover depleted cardiac-specific processes, among other relevant functions, that are undetected by CA. Twenty BA-related microRNAs are identified, and two of them highly heart-enriched that are present in plasma. We describe a microRNA-gene regulatory network related to cardiac processes that are partially validated in vitro and in LV samples from living donors. We prove the higher sensitivity of BA over CA to explain transcriptomic changes in the aging myocardium and report novel molecular insights into human LV biological aging. Our results can find application in future therapeutic and biomarker research

Cxcl12/Cxcr4 signaling controls the migration and process orientation of A9-A10 dopaminergic neurons

CXCL12/CXCR4 signaling has been reported to regulate three essential processes for the establishment of neural networks in different neuronal systems: neuronal migration, cell positioning and axon wiring. However, it is not known whether it regulates the development of A9-A10 tyrosine hydroxylase positive (TH+) midbrain dopaminergic (mDA) neurons. We report here that Cxcl12 is expressed in the meninges surrounding the ventral midbrain (VM), whereas CXCR4 is present in NURR1+ mDA precursors and mDA neurons from E10.5 to E14.5. CXCR4 is activated in NURR1+ cells as they migrate towards the meninges. Accordingly, VM meninges and CXCL12 promoted migration and neuritogenesis of TH+ cells in VM explants in a CXCR4-dependent manner. Moreover, in vivo electroporation of Cxcl12 at E12.5 in the basal plate resulted in lateral migration, whereas expression in the midline resulted in retention of TH+ cells in the IZ close to the midline. Analysis of Cxcr4-/- mice revealed the presence of VM TH+ cells with disoriented processes in the intermediate zone (IZ) at E11.5 and marginal zone (MZ) at E14. Consistently, pharmacological blockade of CXCR4 or genetic deletion of Cxcr4 resulted in an accumulation of TH+ cells in the lateral aspect of the IZ at E14, indicating that CXCR4 is required for the radial migration of mDA neurons in vivo. Altogether, our findings demonstrate that CXCL12/CXCR4 regulates the migration and orientation of processes in A9-A10 mDA neurons.This work was funded by the Swedish Research Council [VR projects: DBRM, 2008:2811, 2011-3116 and 2011-3318]; by the Swedish Foundation for Strategic Research (SRL program); by the Knut and Alice Wallenberg Foundation (CLICK); by the European Commission (NeuroStemcell and DDPD-Genes) and Karolinska Institutet (SFO Thematic Center in Stem cells and Regenerative Medicine) to E.A.; and by the European Commission [mdDANeurodev 222999] to O.M. S.Y. was supported by grants from KID and Chinese Scholarship Council.Peer reviewe

Impacto de la COVID-19 en los servicios de cirugía cardiovascular en España: Análisis de los grupos relacionados con el diagnóstico (Estudio SECCE-COVID-19 fase 2)

Introducción y objetivos La pandemia por COVID-19 causada por infección del virus SARS-CoV-2 ha saturado al sistema sanitario español, afectándose la atención de las enfermedades cardiovasculares. Queremos cuantificar el impacto de la pandemia en el número de las intervenciones quirúrgicas cardíacas analizando los grupos relacionados con el diagnóstico (GRD) más prevalentes de nuestra especialidad. Métodos A instancias de la Sociedad Española de Cirugía Cardiovascular y Endovascular, se solicitó a todos los centros nacionales que quisieron participar, los datos de los códigos de GRD números 162 (cirugía sobre válvulas cardíacas con infarto o diagnóstico complejo), 163 (cirugía sobre válvulas cardíacas sin infarto o diagnóstico complejo), 165 (bypass coronario con infarto o diagnóstico complejo), 166 (bypass coronario sin infarto o diagnóstico complejo) y 167 (otros procedimientos cardiotorácicos o vasculares torácicos) entre el 1 de marzo de 2020 y el 30 de septiembre de 2020 (siete meses), y como período control las mismas fechas de 2019. Resultados Se recibieron los datos de 24 hospitales, 22 públicos y dos privados. Existió un descenso global en el número de intervenciones del 30% (rango -19 a -42%, p < 0,001) de 4.648 en 2019 a 3.262 en 2020 (-1.386 de diferencia), siendo +7% para el GRD 162 (p = 0,500), -37% para el 163 (p = 0,001), -9% para el 165 (p = 0,304), -32% para el 166 (p = 0,001), y -16% para el 167 (p = 0,062). Conclusiones Existió un descenso global de cirugías estadísticamente significativo en 2020 del 30% respecto del 2019 entre el 1 de marzo y el 30 de septiembre

Investigation of the influence of calibration practices on cytogenetic laboratory performance for dose estimation

Purpose: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiation practices in the European biological dosimetry network. Materials and methods: Delivered doses by irradiation facilities used by RENEB partners were determined with EPR/alanine dosimetry system. Dosimeters were irradiated in the same conditions as blood samples. A short survey was also performed to collect the information needed for the data analysis and evaluate the diversity of practices. Results: For most of partners the deviation of delivered dose from the targeted dose remains below 10%. Deviations larger than 10% were observed for five facilities out of 21. Origins of the largest discrepancies were identified. Correction actions were evaluated as satisfactory. The re-evaluation of some ILC results for the fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC) assays has been performed leading to an improvement of the overall performances. Conclusions: This work has shown the importance of dosimetry in radiobiology studies and the needs of harmonization, standardization in irradiation and dosimetry practices and educational training for biologists using ionizing radiation

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

A close link between bacterial community composition and environmental heterogeneity in maritime Antarctic lakes

Seven maritime Antarctic lakes located on Byers Peninsula (Livingston Island, South Shetland Islands) were surveyed to determine the relationship between planktonic bacterial community composition and environmental features. Specifically, the extent to which factors other than low temperature determine the composition of bacterioplankton assemblages of maritime Antarctic lakes was evaluated. Both deep and shallow lakes in the central plateau of the Peninsula, as well as a coastal lake, were studied in order to fully account for the environmental heterogeneity of the Peninsula&rsquo;s lakes. The results showed that shallow coastal lakes display eutrophic conditions, mainly due to the influence of marine animals, whereas plateau lakes are generally deeper and most are oligotrophic, with very limited inputs of nutrients and organic matter. Meso-eutrophic shallow lakes are also present on the Peninsula; they contain microbial mats and a higher trophic status because of the biologically mediated active nutrient release from the sediments. Diversity studies of the lakes&rsquo; planktonic bacterial communities using molecular techniques showed that bacterial diversity is lower in eutrophic than in oligotrophic lakes. The former also differed in community composition with respect to dominant taxa. Multivariate statistical analyses of environmental data yielded the same clustering of lakes as obtained based on the DGGE band pattern after DNA extraction and amplification of 16S rRNA gene fragments. Thus, even in extremely cold lakes, the bacterial community composition parallels other environmental factors, such as those related to trophic status. This correspondence is not only mediated by the influence of marine fauna but also by processes including sediment and ice melting dynamics. The bacterial community can therefore be considered to be equally representative as environmental abiotic variables in demonstrating the environmental heterogeneity among maritime Antarctic lakes. [Int Microbiol 2010; 13(2):67-77

El desarrollo del videojuego Dama: del Medievo a la Modernidad, como medio de formación de estudiantes de enseñanza superior

El presente artículo muestra las actividades realizadas en la Red 5558 “El desarrollo del videojuego Dama: del Medievo a la Modernidad para la formación de estudiantes de enseñanza superior”, perteneciente al Programa Redes ICE de Investigación en docencia universitaria 2021-2022 de la Universidad de Alicante. Dicha Red tiene como objetivos principales (1) la creación de un videojuego de cartas, similar a “Magic”, dotado de una rigurosa base histórica, a partir de las aportaciones de un equipo interdisciplinar formado por docentes y estudiantes de los Grados en Ingeniería Multimedia e Historia de la citada Universidad; y (2) la evaluación de la utilidad del proceso de creación de un videojuego como herramienta didáctica en los procesos universitarios de enseñanza-aprendizaje. El método ha consistido en la creación del equipo de docentes y estudiantes de ambas titulaciones, la asignación de tareas al alumnado, la implementación tutorizada del videojuego, la inclusión de la labor realizada por los estudiantes en sus respectivos trabajos de fin de grado y la recopilación de la opinión del alumnado sobre su aprendizaje en el proyecto por medio de una encuesta y de entrevistas personales. A modo de resultados, se dan a conocer las características del videojuego creado y la evaluación positiva del alumnado sobre el potencial didáctico del trabajo realizado. Y, por último, se plantea una reflexión sobre la posible reorientación de los trabajos de fin de grado en ambas titulaciones