Root Endophyte Colletotrichum tofieldiae Confers Plant Fitness Benefits that Are Phosphate Status Dependent.

A staggering diversity of endophytic fungi associate with healthy plants in nature, but it is usually unclear whether these represent stochastic encounters or provide host fitness benefits. Although most characterized species of the fungal genus Colletotrichum are destructive pathogens, we show here that C. tofieldiae (Ct) is an endemic endophyte in natural Arabidopsis thaliana populations in central Spain. Colonization by Ct initiates in roots but can also spread systemically into shoots. Ct transfers the macronutrient phosphorus to shoots, promotes plant growth, and increases fertility only under phosphorus-deficient conditions, a nutrient status that might have facilitated the transition from pathogenic to beneficial lifestyles. The host's phosphate starvation response (PSR) system controls Ct root colonization and is needed for plant growth promotion (PGP). PGP also requires PEN2-dependent indole glucosinolate metabolism, a component of innate immune responses, indicating a functional link between innate immunity and the PSR system during beneficial interactions with Ct.

The time between Palaeolithic hearths.

Resolving the timescale of human activity in the Palaeolithic Age is one of the most challenging problems in prehistoric archaeology. The duration and frequency of hunter-gatherer camps reflect key aspects of social life and human-environment interactions. However, the time dimension of Palaeolithic contexts is generally inaccurately reconstructed because of the limitations of dating techniques1, the impact of disturbing agents on sedimentary deposits2 and the palimpsest effect3,4. Here we report high-resolution time differences between six Middle Palaeolithic hearths from El Salt Unit X (Spain) obtained through archaeomagnetic and archaeostratigraphic analyses. The set of hearths covers at least around 200-240 years with 99% probability, having decade- and century-long intervals between the different hearths. Our results provide a quantitative estimate of the time framework for the human occupation events included in the studied sequence. This is a step forward in Palaeolithic archaeology, a discipline in which human behaviour is usually approached from a temporal scale typical of geological processes, whereas significant change may happen at the smaller scales of human generations. Here we reach a timescale close to a human lifespan.

Assembly of functional diversity in an oceanic island flora.

Oceanic island floras are well known for their morphological peculiarities and exhibit striking examples of trait evolution1-3. These morphological shifts are commonly attributed to insularity and are thought to be shaped by the biogeographical processes and evolutionary histories of oceanic islands2,4. However, the mechanisms through which biogeography and evolution have shaped the distribution and diversity of plant functional traits remain unclear5. Here we describe the functional trait space of the native flora of an oceanic island (Tenerife, Canary Islands, Spain) using extensive field and laboratory measurements, and relate it to global trade-offs in ecological strategies. We find that the island trait space exhibits a remarkable functional richness but that most plants are concentrated around a functional hotspot dominated by shrubs with a conservative life-history strategy. By dividing the island flora into species groups associated with distinct biogeographical distributions and diversification histories, our results also suggest that colonization via long-distance dispersal and the interplay between inter-island dispersal and archipelago-level speciation processes drive functional divergence and trait space expansion. Contrary to our expectations, speciation via cladogenesis has led to functional convergence, and therefore only contributes marginally to functional diversity by densely packing trait space around shrubs. By combining biogeography, ecology and evolution, our approach opens new avenues for trait-based insights into how dispersal, speciation and persistence shape the assembly of entire native island floras.

The chronology of the human colonization of the Canary Islands.

The human colonization of the Canary Islands represents the sole known expansion of Berber communities into the Atlantic Ocean and is an example of marine dispersal carried out by an African population. While this island colonization shows similarities to the populating of other islands across the world, several questions still need to be answered before this case can be included in wider debates regarding patterns of initial colonization and human settlement, human-environment interactions, and the emergence of island identities. Specifically, the chronology of the first human settlement of the Canary Islands remains disputed due to differing estimates of the timing of its first colonization. This absence of a consensus has resulted in divergent hypotheses regarding the motivations that led early settlers to migrate to the islands, e.g., ecological or demographic. Distinct motivations would imply differences in the strategies and dynamics of colonization; thus, identifying them is crucial to understanding how these populations developed in such environments. In response, the current study assembles a comprehensive dataset of the most reliable radiocarbon dates, which were used for building Bayesian models of colonization. The findings suggest that i) the Romans most likely discovered the islands around the 1st century BCE; ii) Berber groups from western North Africa first set foot on one of the islands closest to the African mainland sometime between the 1st and 3rd centuries CE; iii) Roman and Berber societies did not live simultaneously in the Canary Islands; and iv) the Berber people rapidly spread throughout the archipelago.

Isotope and morphometrical evidence reveals the technological package associated with agriculture adoption in western Europe.

This study aimed to reconstruct the environmental conditions and the crop management practices and plant characteristics when agriculture appeared in western Europe. We analyzed oak charcoal and a large number of cereal caryopsides recovered from La Draga (Girona, Spain), an early (5300 to 4800 cal. BC) agricultural site from the Iberian Peninsula. The carbon isotope discrimination (Δ13C) values of oak, the dominant forest species in the region, indicates prevalence of a wet climate at the site. Further, we reconstructed crop management conditions, achievable yield, and crop characteristics through the analysis of Δ13C, nitrogen isotope composition (δ15N), nitrogen content, and the reconstructed weight of wheat and barley caryopsides, following protocols developed by our team [Araus et al., Nat. Commun. 5, 3953 (2014)] and comparison of these parameters with present-day organic agriculture in the region. In parallel, a regional perspective was achieved through the study of wheat and barley grains of seventeen Neolithic sites from the western Mediterranean. The results suggest that rather than small-garden cultivation, a more extensive agriculture was practiced under good water availability and moderate manuring. Moreover, results from La Draga evidence that grain weight and spike morphology were comparable to contemporary cereals. Growing conditions and the prevalence of improved crop traits indicate that agriculture was fairly consolidated at the time it reached the western edge of Europe.

Effectiveness of a Meningococcal Group B Vaccine (4CMenB) in Children.

BACKGROUND: In September 2015, the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain. METHODS: We conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression. RESULTS: We compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated. CONCLUSIONS: Complete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.

Embracing the diversity of model systems to deconstruct the basis of regeneration and tissue repair.

The eighth EMBO conference in the series 'The Molecular and Cellular Basis of Regeneration and Tissue Repair' took place in Barcelona (Spain) in September 2022. A total of 173 researchers from across the globe shared their latest advances in deciphering the molecular and cellular basis of wound healing, tissue repair and regeneration, as well as their implications for future clinical applications. The conference showcased an ever-expanding diversity of model organisms used to identify mechanisms that promote regeneration. Over 25 species were discussed, ranging from invertebrates to humans. Here, we provide an overview of the exciting topics presented at the conference, highlighting novel discoveries in regeneration and perspectives for regenerative medicine.

The dental proteome of Homo antecessor.

The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated1-5. For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge6-8. Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)9,10 and Homo erectus from Dmanisi (Georgia)1, two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo.

Triadic influence as a proxy for compatibility in social relationships.

Networks of social interactions are the substrate upon which civilizations are built. Often, we create new bonds with people that we like or feel that our relationships are damaged through the intervention of third parties. Despite their importance and the huge impact that these processes have in our lives, quantitative scientific understanding of them is still in its infancy, mainly due to the difficulty of collecting large datasets of social networks including individual attributes. In this work, we present a thorough study of real social networks of 13 schools, with more than 3,000 students and 60,000 declared positive and negative relationships, including tests for personal traits of all the students. We introduce a metric-the "triadic influence"-that measures the influence of nearest neighbors in the relationships of their contacts. We use neural networks to predict the sign of the relationships in these social networks, extracting the probability that two students are friends or enemies depending on their personal attributes or the triadic influence. We alternatively use a high-dimensional embedding of the network structure to also predict the relationships. Remarkably, using the triadic influence (a simple one-dimensional metric) achieves the best accuracy, and adding the personal traits of the students does not improve the results, suggesting that the triadic influence acts as a proxy for the social compatibility of students. We postulate that the probabilities extracted from the neural networks-functions of the triadic influence and the personalities of the students-control the evolution of real social networks, opening an avenue for the quantitative study of these systems.

Understanding the microbiota in the midst of Renaissance architecture and olive groves.

Leading scientists working on the microbiome gathered in an October 2012 meeting in Baeza, Spain, to discuss recent advances in the understanding of the role of the microbiota in immunity, pathogen colonization, metabolism and disease.

Recurrent alcohol-associated hepatitis is common and is associated with increased mortality.

BACKGROUND AND AIMS: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described. APPROACH AND RESULTS: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18]). CONCLUSIONS: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH.

Predictive factors for decompensating events in patients with cirrhosis with primary biliary cholangitis under different lines of therapy.

BACKGROUND AND AIMS: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients. APPROACH AND RESULTS: Multicenter study enrolling 388 patients with PBC-cirrhosis from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and PBC OCA international study of efficacy criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the propensity score-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, clinically significant portal hypertension, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin (OR 0.21 [95% CI: 0.06-0.73]) and AST (OR 0.97 [95% CI: 0.95-0.99]), while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95% CI: 0.95-0.98]). In patients treated with OCA, drug response (sHR 0.23 [95% CI: 0.08-0.64]), diabetes (sHR 5.62 [95% CI: 2.02-15.68]), albumin (sHR 0.34 [95% CI: 0.13-0.89]), and platelets (sHR 0.99 [95% CI: 0.98-1.00]) were related to decompensation. In patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (sHR 3.70 (95% CI: 1.17-11.70]) were associated with decompensated cirrhosis. CONCLUSIONS: Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.

The T-cell repertoire of Spanish patients with COVID-19 as a strategy to link T-cell characteristics to the severity of the disease.

BACKGROUND: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients. METHODS: The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR ß chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19. RESULTS: Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs. CONCLUSIONS: Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome.

Constraints on global mean sea level during Pliocene warmth.

Reconstructing the evolution of sea level during past warmer epochs such as the Pliocene provides insight into the response of sea level and ice sheets to prolonged warming1. Although estimates of the global mean sea level (GMSL) during this time do exist, they vary by several tens of metres2-4, hindering the assessment of past and future ice-sheet stability. Here we show that during the mid-Piacenzian Warm Period, which was on average two to three degrees Celsius warmer than the pre-industrial period5, the GMSL was about 16.2 metres higher than today owing to global ice-volume changes, and around 17.4 metres when thermal expansion of the oceans is included. During the even warmer Pliocene Climatic Optimum (about four degrees Celsius warmer than pre-industrial levels)6, our results show that the GMSL was 23.5 metres above the present level, with an additional 1.6 metres from thermal expansion. We provide six GMSL data points, ranging from 4.39 to 3.27 million years ago, that are based on phreatic overgrowths on speleothems from the western Mediterranean (Mallorca, Spain). This record is unique owing to its clear relationship to sea level, its reliable U-Pb ages and its long timespan, which allows us to quantify uncertainties on potential uplift. Our data indicate that ice sheets are very sensitive to warming and provide important calibration targets for future ice-sheet models7.

Natural selection on the Arabidopsis thaliana genome in present and future climates.

Through the lens of evolution, climate change is an agent of natural selection that forces populations to change and adapt, or face extinction. However, current assessments of the risk of biodiversity associated with climate change1 do not typically take into account how natural selection influences populations differently depending on their genetic makeup2. Here we make use of the extensive genome information that is available for Arabidopsis thaliana and measure how manipulation of the amount of rainfall affected the fitness of 517 natural Arabidopsis lines that were grown in Spain and Germany. This allowed us to directly infer selection along the genome3. Natural selection was particularly strong in the hot-dry location in Spain, where 63% of lines were killed and where natural selection substantially changed the frequency of approximately 5% of all genome-wide variants. A significant portion of this climate-driven natural selection of variants was predictable from signatures of local adaptation (R2 = 29-52%), as genetic variants that were found in geographical areas with climates more similar to the experimental sites were positively selected. Field-validated predictions across the species range indicated that Mediterranean and western Siberian populations-at the edges of the environmental limits of this species-currently experience the strongest climate-driven selection. With more frequent droughts and rising temperatures in Europe4, we forecast an increase in directional natural selection moving northwards from the southern end of Europe, putting many native A. thaliana populations at evolutionary risk.

Guidelines for NGS procedures applied to prenatal diagnosis by the Spanish Society of Gynecology and Obstetrics and the Spanish Association of Prenatal Diagnosis.

OBJECTIVE: This document addresses the clinical application of next-generation sequencing (NGS) technologies for prenatal genetic diagnosis and aims to establish clinical practice recommendations in Spain to ensure uniformity in implementing these technologies into prenatal care. METHODS: A joint committee of expert obstetricians and geneticists was created to review the existing literature on fetal NGS for genetic diagnosis and to make recommendations for Spanish healthcare professionals. RESULTS: This guideline summarises technical aspects of NGS technologies, clinical indications in prenatal setting, considerations regarding findings to be reported, genetic counselling considerations as well as data storage and protection policies. CONCLUSIONS: This document provides updated recommendations for the use of NGS diagnostic tests in prenatal diagnosis. These recommendations should be periodically reviewed as our knowledge of the clinical utility of NGS technologies, applied during pregnancy, may advance.