Changes in the growth rate of Chlamydomonas reinhardtii under long-term selection by temperature and salinity: Acclimation vs. evolution

We investigated the roles of acclimation and different components involved in evolution (adaptation, chance and history) on the changes in the growth rate of the model freshwater microalga Chlamydomonas reinhardtii P. A. Dang. exposed to selective temperature and salinity. Three C. reinhardtii strains previously grown during one year in freshwater medium and 20 °C were exposed to 5 °C temperature increase and a salinity of 5 g L−1 NaCl. Cultures under each selective scenario and in combination (increase of salinity and temperature), were propagated until growth rate achieved an invariant mean value for 6 months (100–350 generations, varying as a function of scenario and strain). The changes of the growth rate under increased temperature were due to both adaptation and acclimation, as well as history. However, acclimation was the only mechanism detected under salinity increase as well as in the selective scenario of both temperature and salinity, suggesting that genetic variability would not allow survival at salinity higher than that to which experimental populations were exposed. Therefore, it could be hypothesized that under a global change scenario an increase in salinity would be a greater challenge than warming for some freshwater phytoplankton.This work was financially supported by the project CGL2017-87314-P (Ministerio de Economía, Industria y Competitividad, Spain) and the project PID2020-118045-GB-I00 (Ministerio de Ciencia e Innovación, Spain). Funding for open access charge: Universidad de Málaga/CBUA

Detection of the maximum resistance to the herbicides diuron and glyphosate, and evaluation of its phenotypic cost, in freshwater phytoplankton

One of the most important anthropogenic impacts on freshwater aquatic ecosystems close to intensive agriculture areas is the cumulative increase in herbicide concentrations. The threat is especially relevant for phytoplankton organisms because they have the same physiological targets as the plants for which herbicides have been designed. This led us to explore the evolutionary response of three phytoplanktonic species to increasing concentrations of two herbicides and its consequences in terms of growth and photosynthesis performance. Specifically, we used an experimental ratchet protocol to investigate the differential evolution and the limit of resistance of a cyanobacterium (Microcystis aeruginosa) and two chlorophyceans (Chlamydomonas reinhardtii and Dictyosphaerium chlorelloides) to two herbicides in worldwide use: glyphosate and diuron. Initially, the growth rate of M. aeruginosa and D. chlorelloides was completely inhibited when they were exposed to a dose of 0.23 ppm diuron or 40 ppm glyphosate, whereas a higher concentration of both herbicides (0.46 ppm diuron or 90 ppm glyphosate) was necessary to abolish C. reinhardtii growth. However, after running a ratchet protocol, the resistance of the three species to both herbicides increased by an adaptation process. M. aeruginosa and D. chlorelloides were able to grow at 1.84 ppm diuron and 80 ppm glyphosate and C. reinhardtii proliferated at twice these concentrations. Herbicide-resistant strains showed lower growth rates than their wild-type coun- terparts in the absence of herbicides, as well as changes on morphology and differences on photosynthetic pigment content. Besides, herbicide-resistant cells generally showed a lower photosynthetic performance than wild-type strains in the three species. These results indicate that the introduction of both herbicides in freshwater ecosystems could produce a diminution of primary production due to the selection of herbicide-resistant mutants, that would exhibit ...This work was financially supported by the project CGL2017-87314- P (Ministerio de Economía, Industria y Competitividad, Spain). The acquisition of the FlowCAM by the University of Málaga was co-financed by the 2008-2011 FEDER program for scientific-technique infrastructure (Proposal number: UNMA08-1E005). Funding for open access charge: Universidad de Málaga/CBUA

What Triggers the Annual Cycle of Cyanobacterium Oscillatoria sp. in an Extreme Environmental Sulfide-Rich Spa?

A seasonal cycle of sulfide, nitrate, phosphate, ammonium, chlorophyll a (Chl a) and Oscillatoria sp. abundance (<100 μm), as well as the relative contribution of taxonomic phytoplanktonic groups (cyanobacteria, green algae, cryptomonads, diatoms and dinoflagellates) to total Chl a were measured by fluorometric measurements at La Hedionda sulfide-rich spa (southern Spain). Fluorometry determined that cyanobacteria Chl a concentration correlated positively with the abundance of Oscillatoria sp. Aggregates at 45–100 μm equivalent spherical diameter (ESD) and was used as an indicator of Oscillatoria sp. Abundance, including for aggregates <45 and >100μm (ESD). In addition, air temperature, radiation and precipitation were downloaded from meteorological databases. In agreement with the meteorological annual cycle observed in air temperature, radiation and precipitation, sulfide concentration at La Hedionda Spa shows an annual cycle with concentrations around 40 μM in winter and up to 200 μM in the dry summer period. Phytoplankton composition was dominated by cyanobacteria (mainly Oscillatoria sp.), but other groups were also represented (green algae, cryptomonads, diatoms and dinoflagellates), although they remained constant throughout the year (median Chl a < 0.2 μg L−1). Cyanobacteria, in contrast, showed an annual cycle with a significantly higher median in summer (Chl a = 1.6 μg L−1) than in winter (Chl a = 0.4 μg L−1). No linear relationship between nutrients and cyanobacteria concentration was observed, but an optimum curve of cyanobacteria concentration to sulfide concentration was fitted through a general additive model (GAM). The four-fold increase of cyanobacteria concentration under exposition of an elevated sulfide concentration can be due to higher growth rates at elevated sulfide concentrations reported for an Oscillatoria sp. strain isolated during the same annual cycle at La Hedionda and we suggest that the selective agent, sulfide, positively triggers Oscillatoria sp. proliferation in summer. According to our findings, the Oscillatoria sp. population of La Hedionda not only is sulfide-resistant, but requires sulfide in its optimal niche

Strategies to design clinical studies to identify predictive biomarkers in cancer research

The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field

Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti–PD-1 for patients with anti–PD-1–refractory tumors

Intratumoral therapies, especially Toll-like receptor agonists, can trigger both the innate and adaptive immune systems. BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid (poly I:C) that induces local and systemic immunotherapeutic effects in mouse models. In a multicenter phase 1 clinical trial, repeated intratumoral administrations of BO-112 induced an increase in tumor cell necrosis and apoptosis, as well as augmented immune reactivity according to gene expression profiling. The first three cohorts receiving BO-112 as a monotherapy resulted in a recommended dose of 1 mg that could be safely repeated. Two grade 3 to 4 adverse reactions in the form of reversible thrombocytopenia were reported. In a fourth cohort of 28 patients with tumors that had primary resistance to anti–programmed cell death protein–1 (PD-1), the combination of intratumoral BO-112 with nivolumab or pembrolizumab was also well tolerated, and 3 patients (2 with melanoma and 1 with renal cell carcinoma) achieved partial responses, with 10 more patients having stable disease at 8 to 12 weeks. Thus, local BO-112 combined with a systemic anti–PD-1 agent might be a strategy to revert anti–PD-1 resistanc

Experiencias de innovación educativa en la Universidad de Murcia (2008)

Resumen tomado de la publicaciónSe recogen diversos proyectos de innovación realizados por el profesorado de la Universidad de Murcia. Son experiencias de adaptación, en las que se han diseñado, aplicado y evaluado diversas acciones de enseñanza, como : el aprendizaje basado en problemas, portafolios, aprendizaje cooperativo, planes de acción tutorial o curso cero de acogida de estudiantes, entre otros. Se trata de dar respuesta al cambio que requiere el proceso de de Convergencia Europea.MurciaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care