Influence of liquid-to-biogas ratio and alkalinity on the biogas upgrading performance in a demo scale algal-bacterial photobioreactor

The influence of the liquid-to-biogas ratio (L/G) and alkalinity on methane quality was evaluated in a 11.7 m3 outdoors horizontal semi-closed tubular photobioreactor interconnected to a 45-L absorption column (AC). CO2 concentrations in the upgraded methane ranged from <0.1 to 9.6% at L/G of 2.0 and 0.5, respectively, with maximum CH4 concentrations of 89.7% at a L/G of 1.0. Moreover, an enhanced CO2 removal (mediating a decrease in CO2 concentration from 9.6 to 1.2%) and therefore higher CH4 contents (increasing from 88.0 to 93.2%) were observed when increasing the alkalinity of the AC cultivation broth from 42 ± 1 mg L−1 to 996 ± 42 mg L−1. H2S was completely removed regardless of the L/G or the alkalinity in AC. The continuous operation of the photobioreactor with optimized operating parameters resulted in contents of CO2 (<0.1%–1.4%), H2S (<0.7 mg m−3) and CH4 (94.1%–98.8%) complying with international regulations for methane injection into natural gas grids.Peer ReviewedPostprint (published version

Modeling GHG emissions, N and C dynamics in Spanish agricultural soils.

To date, only few initiatives have been carried out in Spain in order to use mathematical models (e.g. DNDC, DayCent, FASSET y SIMSNIC) to estimate nitrogen (N) and carbon (C) dynamics as well as greenhouse gases (GHG) in Spanish agrosystems. Modeling at this level may allow to gain insight on both the complex relationships between biological and physicochemical processes, controlling the processes leading to GHG production and consumption in soils (e.g. nitrification, denitrification, decomposing, etc.), and the interactions between C and N cycles within the different components of the continuum plant-soil-environment. Additionally, these models can simulate the processes behind production, consumition and transport of GHG (e.g. nitrous oxide, N2O, and carbon dioxide, CO2) in the short and medium term and at different scales. Other sources of potential pollution from soils can be identified and quantified using these process-based models (e.g. NO3 y NH3)

Benefit with preventive noninvasive ventilation in subgroups of patients at high-risk for reintubation: a post hoc analysis.

Background: High-flow nasal cannula (HFNC) was shown to be non-inferior to noninvasive ventilation (NIV) for preventing reintubation in a general population of high-risk patients. However, some subgroups of high-risk patients might benefit more from NIV. We aimed to determine whether the presence of many risk factors or overweight (body mass index (BMI) ≥ 25 kg/m2) patients could have different response to any preventive therapy, NIV or HFNC in terms of reduced reintubation rate. Methods: Not pre-specified post hoc analysis of a multicentre, randomized, controlled, non-inferiority trial comparing NFNC and NIV to prevent reintubation in patients at risk for reintubation. The original study included patients with at least 1 risk factor for reintubation. Results: Among 604 included in the original study, 148 had a BMI ≥ 25 kg/m2. When adjusting for potential covariates, patients with ≥ 4 risk factors (208 patients) presented a higher risk for reintubation (OR 3.4 [95%CI 2.16–5.35]). Patients with ≥ 4 risk factors presented lower reintubation rates when treated with preventive NIV (23.9% vs 45.7%; P = 0.001). The multivariate analysis of overweight patients, adjusted for covariates, did not present a higher risk for reintubation (OR 1.37 [95%CI 0.82–2.29]). However, those overweight patients presented an increased risk for reintubation when treated with preventive HFNC (OR 2.47 [95%CI 1.18–5.15]). Conclusions: Patients with ≥ 4 risk factors for reintubation may benefit more from preventive NIV. Based on this result, HFNC may not be the optimal preventive therapy in overweight patients. Specific trials are needed to confirm these results.post-print916 K

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non‐invasive biomarkers to detect early kidney damage and the onset of a senescent phenotype are lacking. Most of the preclinical senescence studies in aging have been done in very old mice. Furthermore, the precise characterization and over-time development of age-related senes-cence in the kidney remain unclear. To address these limitations, the age-related activation of cellular senescence-associated mechanisms and their correlation with early structural changes in the kidney were investigated in 3- to 18-month-old C57BL6 mice. Inflammatory cell infiltration was ob-served by 12 months, whereas tubular damage and collagen accumulation occurred later. Early activation of cellular-senescence-associated mechanisms was found in 12-month-old mice, character-ized by activation of the DNA-damage-response (DDR), mainly in tubular cells; activation of the antioxidant NRF2 pathway; and klotho downregulation. However, induction of tubular-cell-cycle-arrest (CCA) and overexpression of renal senescent-associated secretory phenotype (SASP) components was only found in 18-month-old mice. In aging mice, both inflammation and oxidative stress (marked by elevated lipid peroxidation and NRF2 inactivation) remained increased. These findings support the hypothesis that prolonged DDR and CCA, loss of nephroprotective factors (klotho), and dysfunctional redox regulatory mechanisms (NRF2/antioxidant defense) can be early drivers of age-related kidney-damage progressionThis research was funded by grants from the Instituto de Salud Carlos III (ISCIII); Fondos FEDER European Union (PI17/00119, PI20/00140; and DTS20/00083 to M.R.-O.; PI18/01133 to A.M.R.); Sara Borrell’ program from Instituto de Salud Carlos III (ISCIII) (grant number CD20/00042 to R.R.R.-D.); Red de Investigación Renal REDINREN: RD16/0009/0003 and RICORS program to RICORS2040 496 (RD21/0005), to M.R.-O., Sociedad Española de Nefrología; “NOVELREN-CM: Enfermedad renal crónica: nuevas Estrategias para la prevención, Diagnóstico y tratamiento” (B2017/BMD3751 to M.R.-O.); “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O.); Juan de la Cierva incorporacion grant: IJC2018-035187-I to S.R.-M.; innovation program under the Marie Skłodowska-Curie grant of the European Union’s Horizon 2020 (IMProvePD ID: 812699) to M.R.-O.; and Fundacion Conchita Rabago to L.T.-

Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis

Crescentic glomerulonephritis is a devastating autoimmune disease that without early and properly treatment may rapidly progress to end-stage renal disease and death. Current immunosuppressive treatment provides limited efficacy and an important burden of adverse events. Epigenetic drugs are a source of novel therapeutic tools. Among them, bromodomain and extraterminal domain (BET) inhibitors (iBETs) block the interaction between bromodomains and acetylated proteins, including histones and transcription factors. iBETs have demonstrated protective effects on malignancy, inflammatory disorders and experimental kidney disease. Recently, Gremlin-1 was proposed as a urinary biomarker of disease progression in human anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. We have now evaluated whether iBETs could regulate Gremlin-1 in experimental anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS) in mice, a model resembling human crescentic glomerulonephritis. In NTS-injected mice, the iBET JQ1 inhibited renal Gremlin-1 overexpression and diminished glomerular damage, restoring podocyte numbers. Chromatin immunoprecipitation assay demonstrated BRD4 enrichment of the Grem-1 gene promoter in injured kidneys, consistent with Gremlin-1 epigenetic regulation. Moreover, JQ1 blocked BRD4 binding and inhibited Grem-1 gene transcription. The beneficial effect of iBETs was also mediated by modulation of NOTCH pathway. JQ1 inhibited the gene expression of the NOTCH effectors Hes-1 and Hey-1 in NTS-injured kidneys. Our results further support the role for epigenetic drugs, such as iBETs, in the treatment of rapidly progressive crescentic glomerulonephritis

Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes

Acute kidney injury (AKI) is more frequent in elderly patients. Mechanisms contributing to AKI (tubular cell death, inflammatory cell infiltration, impaired mitochondrial function, and prolonged cell-cycle arrest) have been linked to cellular senescence, a process implicated in regeneration failure and progression to fibrosis. However, the molecular and pathological basis of the age-related increase in AKI incidence is not completely understood. To explore these mechanisms, experimental AKI was induced by folic acid (FA) administration in young (3-months-old) and old (1-year-old) mice, and kidneys were evaluated in the early phase of AKI, at 48 h. Tubular damage score, KIM-1 expression, the recruitment of infiltrating immune cells (mainly neutrophils and macrophages) and proinflammatory gene expression were higher in AKI kidneys of old than of young mice. Tubular cell death in FA-AKI involves several pathways, such as regulated necrosis and apoptosis. Ferroptosis and necroptosis cell-death pathways were upregulated in old AKI kidneys. In contrast, caspase-3 activation was only found in young but not in old mice. Moreover, the antiapoptotic factor BCL-xL was significantly overexpressed in old, injured kidneys, suggesting an age-related apoptosis suppression. AKI kidneys displayed evidence of cellular senescence, such as increased levels of cyclin dependent kinase inhibitors p16ink4a and p21cip1, and of the DNA damage response marker γH2AX. Furthermore, p21cip1 mRNA expression and nuclear staining for p21cip1 and γH2AX were higher in old than in young FA-AKI mice, as well as the expression of senescence-associated secretory phenotype (SASP) components (Il-6, Tgfb1, Ctgf, and Serpine1). Interestingly, some infiltrating immune cells were p21 or γH2AX positive, suggesting that molecular senescence in the immune cells (“immunosenescence”) are involved in the increased severity of AKI in old mice. In contrast, expression of renal protective factors was dramatically downregulated in old AKI mice, including the antiaging factor Klotho and the mitochondrial biogenesis driver PGC-1α. In conclusion, aging resulted in more severe AKI after the exposure to toxic compounds. This increased toxicity may be related to magnification of proinflammatory-related pathways in older mice, including a switch to a proinflammatory cell death (necroptosis) instead of apoptosis, and overactivation of cellular senescence of resident renal cells and infiltrating inflammatory cells

Statins: Could an old friend help the fight against COVID-19?

This is the peer reviewed version of the following article: "Statins: Could an old friend help the fight against COVID-19?" . British Journal of Pharmacology (2020): 19 June, which has been published in final form at https://doi.org/10.1111/bph.15166. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versionshe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomesThis work and data discussed here were supported by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119 and Red de Investigación Renal (REDINREN): RD16/0009, to M.R-O, PI17/01495 to J.E, PI18/01133 to AMR, PI19/00815 to A.O); Comunidad de Madrid (“NOVELREN” B2017/BMD3751 to M.R-O, B2017/BMD-3686 CIFRA2-CM to A.O); Spanish Ministry of Economy and Competitiveness MINECO (DTS17/00203, DTS19/00093) to J,E; “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R-O and SR-M); ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071) and DTS18/00032 to A.O; The “Sara Borrell” postdoctoral training program of the ISCIII supported the salary of SR-M (CD19/00021), IMPROVE-PD project (“Identification and Management of Patients at Risk–Outcome and Vascular Events in Peritoneal Dialysis”) funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 812699 to M.R.O

Geoarchaeological studies of sources and lithic quarries in the Pampean Sierras and adjacent plains

El material lítico es el elemento de mayor abundancia en los registros arqueológicos de Sierras Centrales y sus llanuras adyacentes. Los estudios realizados sobre el mismo utilizan diferentes escalas espaciales, metodologías de campo y laboratorio. Sin embargo, los programas de investigación orientados a la detección de fuentes de aprovisionamiento y canteras arqueológicas no tienen en la región un desarrollo similar al de otras regiones del Argentina. En este trabajo se presentan las líneas iniciales de un proyecto de escala macrorregional, específicamente orientado a su estudio. Los resultados alcanzados hasta el momento permitieron identificar numerosas canteras y fuentes en las provincias de San Luis, Córdoba, La Rioja y Catamarca. En ese marco, proponemos un modelo de yacencia de rocas silíceas. El mismo permite entender por un lado la génesis de las rocas identificadas y, por otra parte, se constituye como el primer modelo predictivo de escala amplia para el centro de Argentina.Lithic materials are among the most abundant items in the archaeological record of the Central Ranges and their adjacent plains. The studies carried out with lithic artefacts use different spatial scales, as well as field and laboratory methodologies. However, the research programs oriented to the detection of lithic sources and archaeological quarries do not have in this region a similar development in comparison to other regions of Argentina. This paper presents the initial lines of a macroregional scale project, specifically oriented to their study. The results achieved so far allowed the identification of numerous quarries and lithic sources in San Luis, Córdoba, La Rioja, and Catamarca provinces. We propose a model of deposit of the siliceous rocks which allows to understand the genesis of the identified rocks. On the other hand, it is the first wide-scale predictive occurrence model for the center of Argentina.Fil: Heider, Guillermo. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: Ortiz Suarez, Ariel. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; ArgentinaFil: Rivero, Diego Eduardo. Centro de Estudios Históricos "Profesor Carlos S. A. Segreti". Instituto de Estudios Históricos - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Estudios Históricos; ArgentinaFil: Baldo, Edgardo Gaspar Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Pastor, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Catamarca. Universidad Nacional de Catamarca. Centro de Investigaciones y Transferencia de Catamarca; ArgentinaFil: Ramos, Gabriel. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; ArgentinaFil: Borgo, Mariangeles. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: Gil, Raul Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Chiesa, Jorge. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; ArgentinaFil: Costa, Carlos. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; ArgentinaFil: Recalde, Maria Andrea. Centro de Estudios Historicos "prof. Carlos S.a. Segreti". Instituto de Estudios Historicos. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Estudios Historicos.; ArgentinaFil: Curtoni, Rafael Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Capriolo, Ana Julieta. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: Muñoz, Lucas. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; Argentin

Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes

Acute kidney injury (AKI) is more frequent in elderly patients. Mechanisms contributing to AKI (tubular cell death, inflammatory cell infiltration, impaired mitochondrial function, and prolonged cell-cycle arrest) have been linked to cellular senescence, a process implicated in regeneration failure and progression to fibrosis. However, the molecular and pathological basis of the age-related increase in AKI incidence is not completely understood. To explore these mechanisms, experimental AKI was induced by folic acid (FA) administration in young (3-months-old) and old (1-year-old) mice, and kidneys were evaluated in the early phase of AKI, at 48 h. Tubular damage score, KIM-1 expression, the recruitment of infiltrating immune cells (mainly neutrophils and macrophages) and proinflammatory gene expression were higher in AKI kidneys of old than of young mice. Tubular cell death in FA-AKI involves several pathways, such as regulated necrosis and apoptosis. Ferroptosis and necroptosis cell-death pathways were upregulated in old AKI kidneys. In contrast, caspase-3 activation was only found in young but not in old mice. Moreover, the antiapoptotic factor BCL-xL was significantly overexpressed in old, injured kidneys, suggesting an age-related apoptosis suppression. AKI kidneys displayed evidence of cellular senescence, such as increased levels of cyclin dependent kinase inhibitors p16ink4a and p21cip1, and of the DNA damage response marker γH2AX. Furthermore, p21cip1 mRNA expression and nuclear staining for p21cip1 and γH2AX were higher in old than in young FA-AKI mice, as well as the expression of senescence-associated secretory phenotype (SASP) components (Il-6, Tgfb1, Ctgf, and Serpine1). Interestingly, some infiltrating immune cells were p21 or γH2AX positive, suggesting that molecular senescence in the immune cells (“immunosenescence”) are involved in the increased severity of AKI in old mice. In contrast, expression of renal protective factors was dramatically downregulated in old AKI mice, including the antiaging factor Klotho and the mitochondrial biogenesis driver PGC-1α. In conclusion, aging resulted in more severe AKI after the exposure to toxic compounds. This increased toxicity may be related to magnification of proinflammatory-related pathways in older mice, including a switch to a proinflammatory cell death (necroptosis) instead of apoptosis, and overactivation of cellular senescence of resident renal cells and infiltrating inflammatory cells