Potential use of Sargassum muticum as source of plant biostimulants after three different drying methods

Seaweed derived biostimulants are gaining attention as an important tool in sustainable agriculture. This offers a unique opportunity to alleviate the environmental impact of Sargassum muticum (Ochrophyta, Phaeophyceae) as an invasive species by finding new applications for its biomass. In this sense, incorporating green extraction technologies is fundamental to ensure environmental-friendly goals. This research was initiated in an attempt to contribute to an integral valorization system of S. muticum biomass, exploring the biostimulant potential of the solubles obtained from pressed solids, through an autohydrolysis treatment. In addition, we compared the effect of three different liquid phase drying techniques (spray-drying, freeze-drying and convective air-drying). Low stress drying techniques as spray-drying showed better conservation of bioactive compounds and biostimulant potential. A bioassay with Nastrium officinale showed no phytotoxic effects despite high electric conductivity in most of the extracts and concentrations. Dried extracts showed mainly an amorphous structure but occasional crystal formation when spray-dried at low temperatures (T out  = 50 ºC) and after convective air drying (T = 40 ºC). Significant increases in root development were achieved at a concentration of 5 mg L −1 of spray-dried extracts and 50 mg L −1 in case of freeze-dried extracts. Munoo-Liisa vitality index showed best results with 50 mg L −1 of freeze-dried extracts. This study provides important information about the influence of different drying techniques on the physicochemical properties and biostimulant potential of S. muticum aqueous extracts and contributes to the integral valorization of its biomass.Agencia Estatal de Investigación | Ref. RYC2018-024454-IXunta de Galicia | Ref. ED431F 2020/01Xunta de Galicia | Ref. ED481D-2022/018Universidade de Vigo/CISU

Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients

Mitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts: a meta-analysis and functional study

Extended report[Abstract] Objective To evaluate the influence of the mitochondrial DNA (mtDNA) haplogroups in the risk of incident knee osteoarthritis (OA) and to explain the functional consequences of this association to identify potential diagnostic biomarkers and therapeutic targets. Methods Two prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 2579 subjects of the incidence subcohort, and the cohort hip and cohort knee (CHECK) included 635, both with 8-year follow-up. The analysis included the association of mtDNA haplogroups with the rate of incident knee OA in subjects from both cohorts followed by a subsequent meta-analysis. Transmitochondrial cybrids harbouring haplogroup J or H were constructed to detect differences between them in relation to physiological features including specific mitochondrial metabolic parameters, reactive oxygen species production, oxidative stress and apoptosis. Results Compared with H, the haplogroup J associates with decreased risk of incident knee OA in subjects from OAI (HR=0.680; 95% CI 0.470 to 0.968; p<0.05) and CHECK (HR=0.728; 95% CI 0.469 to 0.998; p<0.05). The subsequent meta-analysis including 3214 cases showed that the haplogroup J associates with a lower risk of incident knee OA (HR=0.702; 95% CI 0.541 to 0.912; p=0.008). J cybrids show a lower free radical production, higher cell survival under oxidative stress conditions, lower grade of apoptosis as well as lower expression of the mitochondrially related pro-apoptotic gene BCL2 binding component 3 (BBC3). In addition, J cybrids also show a lower mitochondrial respiration and glycolysis leading to decreased ATP production. Conclusions The physiological effects of the haplogroup J are beneficial to have a lower rate of incident knee OA over time. Potential drugs to treat OA could focus on emulating the mitochondrial behaviour of this haplogroup.Instituto de Salud Carlos III; CIBERCB06/01/0040-SpainInstituto de Salud Carlos III; RETIC-RIER-RD12/0009/0018Instituto de Salud Carlos III; PI14/01254Instituto de Salud Carlos III; CP12/0319

Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing

Objetives The aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance. Methods Using Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016. Results Among 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87). Conclusions NGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.Funding: M.A.M. was supported in part by: Agency for Health Technology Assessment and Research Supported by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (PS12/02131 and PI17/02150); Agència de Gestió d´Ajuts Universitaris I de Recerca, Generalitat de Catalunya, 2017 SGR 794; and Fundació Marató TV3 project code 201824

Open Peer Review Module for Open Access Repositories

Presentamos el primer módulo de revisión por pares abierto para repositorios de acceso abierto. El módulo, diseñado en esta primera etapa para la integración con repositorios DSpace, para evitar ‘endogamia’, permite a cualquier especialista ofrecer una evaluación cualitativa y cuantitativa de cualquier trabajo de investigación alojado en un repositorio compatible. El sistema se apoya en el uso de métricas ponderadas de reputación para artículos, revisiones, autores y revisores. Una función de búsqueda avanzada permite a los usuarios del repositorio filtrar u ordenar los trabajos de investigación por su reputación, que se calcula basándose en las revisiones que recibe. La integración de la revisión por pares en los repositorios promueve la discusión abierta al permitir una colaboración directa, abierta y transparente entre los autores y los revisores, y produce nuevas métricas que reflejan directamente la calidad de un trabajo de investigación percibida por los colegas expertos, al contrario que las métricas actuales disponibles que dan cuenta de la calidad solo de manera indirecta a través de las estadísticas de uso. El sistema de revisión por pares implementado permite que los revisores de un trabajo y los autores del mismo (derecho de réplica) que estén en la base de datos del repositorio pueden hacer comentarios sobre las revisiones del trabajo. Esta es una opción que podría ser ampliada a todos los especialistas en la materia registrados en el repositorio pero sin tenerlos en cuenta en las métricas. El módulo de revisión por pares en abierto ya se ha instalado en dos importantes repositorios españoles (DIGITAL.CSIC, e-IEO) con resultados iniciales prometedores.We present the first open peer review module for open access repositories. The module, designed in this first stage for integration with DSpace repositories, in order to avoid “inbreeding”, enables any scholar to offer a qualitative and quantitative evaluation of any research object hosted in a compliant repository. Weighted reputation metrics are calculated for articles, reviews, authors and reviewers. An advanced search function allows repository users to filter or sort research objects based on their reputation, which it is calculated based on the reviews received. The integration of peer review in repositories promotes open scholarship by enabling a direct, open and transparent collaboration between authors and reviewers, and produces novel metrics directly reflecting the perceived quality of a research work by expert peers, contrary to current available metrics that only indirectly account for quality through usage statistics. Reviewers of the work and the authors of the work (right of reply) at the repository data base can comment on the reviews of that work. This option may be extended to all specialists in the field registered at the repository but without taking them into account in metrics. The open peer review module has already been installed in two major Spanish repositories (DIGITAL.CSIC, e-IEO) with promising initial results.OpenAIR

Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO

AbstractThoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets.</jats:p

Age and date for early arrival of the Acheulian in Europe (Barranc de la Boella, la Canonja, Spain)

The first arrivals of hominin populations into Eurasia during the Early Pleistocene are currently considered to have occurred as short and poorly dated biological dispersions. Questions as to the tempo and mode of these early prehistoric settlements have given rise to debates concerning the taxonomic significance of the lithic assemblages, as trace fossils, and the geographical distribution of the technological traditions found in the Lower Palaeolithic record. Here, we report on the Barranc de la Boella site which has yielded a lithic assemblage dating to ,1 million years ago that includes large cutting tools (LCT). We argue that distinct technological traditions coexisted in the Iberian archaeological repertoires of the late Early Pleistocene age in a similar way to the earliest sub-Saharan African artefact assemblages. These differences between stone tool assemblages may be attributed to the different chronologies of hominin dispersal events. The archaeological record of Barranc de la Boella completes the geographical distribution of LCT assemblages across southern Eurasia during the EMPT (Early-Middle Pleistocene Transition, circa 942 to 641 kyr). Up to now, chronology of the earliest European LCT assemblages is based on the abundant Palaeolithic record found in terrace river sequences which have been dated to the end of the EMPT and later. However, the findings at Barranc de la Boella suggest that early LCT lithic assemblages appeared in the SW of Europe during earlier hominin dispersal episodes before the definitive colonization of temperate Eurasia took place.The research at Barranc de la Boella has been carried out with the financial support of the Spanish Ministerio de Economı´a y Competitividad (CGL2012- 36682; CGL2012-38358, CGL2012-38434-C03-03 and CGL2010-15326; MICINN project HAR2009-7223/HIST), Generalitat de Catalunya, AGAUR agence (projects 2014SGR-901; 2014SGR-899; 2009SGR-324, 2009PBR-0033 and 2009SGR-188) and Junta de Castilla y Leo´n BU1004A09. Financial support for Barranc de la Boella field work and archaeological excavations is provided by the Ajuntament de la Canonja and Departament de Cultura (Servei d’Arqueologia i Paleontologia) de la Generalitat de Catalunya. A. Carrancho’s research was funded by the International Excellence Programme, Reinforcement subprogramme of the Spanish Ministry of Education. I. Lozano-Ferna´ndez acknowledges the pre-doctoral grant from the Fundacio´n Atapuerca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

El barranc de la Boella de la Canonja (Tarragonès) revisitat en la intervenció arqueològica preventiva de l'any 2007

El barranc de la Boella de la Canonja és un jaciment descobert en el primer terç del segle XX. Cinquanta anys després de la seva descoberta, la publicació d'aquest jaciment pels senyors R. Capdevila i S. Vilaseca va permetre actualitzar l'escàs coneixement de la bioestratigrafia del quaternari del Camp de Tarragona (Vilaseca, 1973). Tal com assenyala el mateix S. Vilaseca, la presència de fòssils de mamífers en el barranc va ser donada a conèixer per J. R. Bataller en la memòria explicativa del segon mapa geològic del full 473 de l'IGME corresponent a Tarragona (Bataller, 1935). El mateix S. Vilaseca apunta altres descobertes de mamífers ressenyades en el Camp de Tarragona, com la nota de Faura i Sans sobre un fragment de molar de proboscidi que Harlé determinaria com Elephas meridionalis el mateix any (Faura i Sans, 1920; Harlé, 1920). Aquesta resta va ser enviada per A. Romaní, aleshores director del Museu Balaguer de Vilanova i la Geltrú, a qui li van fer arribar des d'unes pedreres del Port de Tarragona. Els treballs geològics de M. Faura i Sans, J.R. Bataller i S. Vilaseca durant el primer quart del segle XX protagonitzaren el desenvolupament de la geologia, la paleontologia i la prehistòria en el marc del Servei del Mapa de la Mancomunitat de Catalunya

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)