Innate chemical, but not visual, threat cues have been co‐opted as unconditioned stimulus for social fear learning in zebrafish

Animals can use social information to detect threat in the environment. In particular, social learning allows animals to learn about dangers without incurring in the costs of trial-and-error learning. In zebrafish, both chemical and visual social cues elicit an innate alarm response, which consists of erratic movement followed by freezing behavior. Injured zebrafish release an alarm substance from their skin that elicits the alarm response. Similarly, the sight of conspecifics displaying the alarm response can also elicit the expression of this response in observers. In this study, we investigated if these social cues of danger can also be used by zebrafish as unconditioned stimulus (US) in learning. We found that only the chemical cue was effective in the social fear conditioning. We suggest that this differential efficacy of social cues results from the fact that the alarm cue is a more reliable indicator of threat, than the sight of an alarmed conspecific. Therefore, although multiple social cues may elicit innate responses not all have been evolutionarily co-opted to act as US in associative learning. Furthermore, the use of the expression of the immediate early genes as markers of neuronal activity showed that chemical social fear conditioning is paralleled by a differential activation of the olfactory bulbs and by a different pattern of functional connectivity across brain regions involved in olfactory processing.FCT - Fundação para a Ciência e Tecnologiainfo:eu-repo/semantics/publishedVersio

Closing Water Cycles in the Built Environment through Nature-Based Solutions: The Contribution of Vertical Greening Systems and Green Roofs

Water in the city is typically exploited in a linear process, in which most of it is polluted, treated, and discharged; during this process, valuable nutrients are lost in the treatment process instead of being cycled back and used in urban agriculture or green space. The purpose of this paper is to advance a new paradigm to close water cycles in cities via the implementation of naturebased solutions units (NBS_u), with a particular focus on building greening elements, such as green roofs (GRs) and vertical greening systems (VGS). The hypothesis is that such “circular systems” can provide substantial ecosystem services and minimize environmental degradation. Our method is twofold: we first examine these systems from a life-cycle point of view, assessing not only the inputs of conventional and alternative materials, but the ongoing input of water that is required for irrigation. Secondly, the evapotranspiration performance of VGS in Copenhagen, Berlin, Lisbon, Rome, Istanbul, and Tel Aviv, cities with different climatic, architectural, and sociocultural contexts have been simulated using a verticalized ET0 approach, assessing rainwater runoff and greywater as irrigation resources. The water cycling performance of VGS in the mentioned cities would be sufficient at recycling 44% (Lisbon) to 100% (Berlin, Istanbul) of all accruing rainwater roof–runoff, if water shortages in dry months are bridged by greywater. Then, 27–53% of the greywater accruing in a building could be managed on its greened surface. In conclusion, we address the gaps in the current knowledge and policies identified in the different stages of analyses, such as the lack of comprehensive life cycle assessment studies that quantify the complete “water footprint” of building greening systems.info:eu-repo/semantics/publishedVersio

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among comorbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. Conclusions: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registration: NCT02350348

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BACKGROUND: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. METHODS: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. RESULTS: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. CONCLUSIONS: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event

The drivers and impacts of Amazon forest degradation

BACKGROUND: Most analyses of land-use and land-cover change in the Amazon forest have focused on the causes and effects of deforestation. However, anthropogenic disturbances cause degradation of the remaining Amazon forest and threaten their future. Among such disturbances, the most important are edge effects (due to deforestation and the resulting habitat fragmentation), timber extraction, fire, and extreme droughts that have been intensified by human-induced climate change. We synthesize knowledge on these disturbances that lead to Amazon forest degradation, including their causes and impacts, possible future extents, and some of the interventions required to curb them. ADVANCES: Analysis of existing data on the extent of fire, edge effects, and timber extraction between 2001 and 2018 reveals that 0.36 ×106 km2 (5.5%) of the Amazon forest is under some form of degradation, which corresponds to 112% of the total area deforested in that period. Adding data on extreme droughts increases the estimate of total degraded area to 2.5 ×106 km2, or 38% of the remaining Amazonian forests. Estimated carbon loss from these forest disturbances ranges from 0.05 to 0.20 Pg C year−1 and is comparable to carbon loss from deforestation (0.06 to 0.21 Pg C year−1). Disturbances can bring about as much biodiversity loss as deforestation itself, and forests degraded by fire and timber extraction can have a 2 to 34% reduction in dry-season evapotranspiration. The underlying drivers of disturbances (e.g., agricultural expansion or demand for timber) generate material benefits for a restricted group of regional and global actors, whereas the burdens permeate across a broad range of scales and social groups ranging from nearby forest dwellers to urban residents of Andean countries. First-order 2050 projections indicate that the four main disturbances will remain a major threat and source of carbon fluxes to the atmosphere, independent of deforestation trajectories. OUTLOOK: Whereas some disturbances such as edge effects can be tackled by curbing deforestation, others, like constraining the increase in extreme droughts, require additional measures, including global efforts to reduce greenhouse gas emissions. Curbing degradation will also require engaging with the diverse set of actors that promote it, operationalizing effective monitoring of different disturbances, and refining policy frameworks such as REDD+. These will all be supported by rapid and multidisciplinary advances in our socioenvironmental understanding of tropical forest degradation, providing a robust platform on which to co-construct appropriate policies and programs to curb it

The drivers and impacts of Amazon forest degradation

Approximately 2.5 × 10 6 square kilometers of the Amazon forest are currently degraded by fire, edge effects, timber extraction, and/or extreme drought, representing 38% of all remaining forests in the region. Carbon emissions from this degradation total up to 0.2 petagrams of carbon per year (Pg C year −1 ), which is equivalent to, if not greater than, the emissions from Amazon deforestation (0.06 to 0.21 Pg C year −1 ). Amazon forest degradation can reduce dry-season evapotranspiration by up to 34% and cause as much biodiversity loss as deforestation in human-modified landscapes, generating uneven socioeconomic burdens, mainly to forest dwellers. Projections indicate that degradation will remain a dominant source of carbon emissions independent of deforestation rates. Policies to tackle degradation should be integrated with efforts to curb deforestation and complemented with innovative measures addressing the disturbances that degrade the Amazon forest

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery