The holocentric chromosome microevolution: From phylogeographic patterns to genomic associations with environmental gradients.

Geographic isolation and chromosome evolution are two of the major drivers of diversification in eukaryotes in general, and specifically, in plants. On one hand, range shifts induced by Pleistocene glacial oscillations deeply shaped the evolutionary trajectories of species in the Northern Hemisphere. On the other hand, karyotype variability within species or species complexes may have adaptive potential as different karyotypes may represent different recombination rates and linkage groups that may be associated with locally adapted genes or supergenes. Organisms with holocentric chromosomes are ideal to study the link between local adaptation and chromosome evolution, due to their high cytogenetic variability, especially when it seems to be related to environmental variation. Here, we integrate the study of the phylogeography, chromosomal evolution and ecological requirements of a plant species complex distributed in the Western Euro-Mediterranean region (Carex gr. laevigata, Cyperaceae). We aim to clarify the relative influence of these factors on population differentiation and ultimately on speciation. We obtained a well-resolved RADseq phylogeny that sheds light on the phylogeographic patterns of molecular and chromosome number variation, which are compatible with south-to-north postglacial migration. In addition, landscape genomics analyses identified candidate loci for local adaptation, and also strong significant associations between the karyotype and the environment. We conclude that karyotype distribution in C. gr. laevigata has been constrained by both range shift dynamics and local adaptation. Our study demonstrates that chromosome evolution may be responsible, at least partially, for microevolutionary patterns of population differentiation and adaptation in Carex.

Alternative Modes of Introgression-Mediated Selection Shaped Crop Adaptation to Novel Climates.

Recent plant genomic studies provide fine-grained details on the evolutionary consequences of adaptive introgression during crop domestication. Modern genomic approaches and analytical methods now make it possible to better separate the introgression signal from the demographic signal thus providing a more comprehensive and complex picture of the role of introgression in local adaptation. Adaptive introgression has been fundamental for crop expansion and has involved complex patterns of gene flow. In addition to providing new and more favorable alleles of large effect, introgression during the early stages of domestication also increased allelic diversity at adaptive loci. Previous studies have largely underestimated the effect of such increased diversity following introgression. Recent genomic studies in wheat, potato, maize, grapevine, and ryegrass show that introgression of multiple genes, of as yet unknown effect, increased the effectiveness of purifying selection, and promoted disruptive or fluctuating selection in early cultivars and landraces. Historical selection processes associated with introgression from crop wild relatives provide an instructive analog for adaptation to current climate change and offer new avenues for crop breeding research that are expected to be instrumental for strengthening food security in the coming years.

Moving towards the ecological intensification of tree plantations.

The growing demand for timber and the boom in massive tree-planting programs could mean the spreading of mismanaged tree plantations worldwide. Here, we apply the concept of ecological intensification to forestry systems as a viable biodiversity-focused strategy that could be critical to develop productive, yet sustainable, tree plantations. Tree plantations can be highly productive if tree species are properly combined to complement their ecological functions. Simultaneously considering soil biodiversity and animal-mediated biocontrol will be critical to minimize the reliance on external inputs. Integrating genetic, functional, and demographic diversity across heterogeneous landscapes should improve resilience under climate change. Designing ecologically intensified plantations will mean breaking the timber productivity versus conservation dichotomy and assuring the maintenance of key ecosystem services at safe levels.

Incidencia y características de las caídas de pacientes hospitalizados: estudio de cohortes / Incidence and characteristics of falls in hospitalized patients: A cohort study

Objetivo: Estimar la incidencia de caídas y conocer sus características en cuanto a localización, temporalidad y lesiones producidas, y analizar las características sociodemográficas y clínicas de los pacientes que sufren caídas. Método: Se llevó a cabo un estudio observacional de cohortes retrospectivo, en un hospital de nivel 2 del Servicio Madrileño de Salud. Se estudiaron las caídas de pacientes hospitalizados entre el 1 de julio de 2018 y el 30 de junio de 2019. Se estimó la tasa de incidencia de caídas por 1.000 días de estancia considerando una distribución de Poisson. Se describen las características de las caídas: temporalidad, lesiones producidas, localización de las lesiones y pauta de fármacos. Se registraron características sociodemográficas y clínicas de los pacientes que sufrieron una caída. Se realizó un análisis univariante para comparar los resultados por sexos. Todos los datos se han obtenido de registros de la historia clínica electrónica. Resultados: Se estudiaron 132 caídas, que suponen una tasa de 1,61 caídas por 1.000 días de estancia. Hombres, edad avanzada e ingreso a cargo de una especialidad médica presentaron una tasa de caída significativamente mayor. Los pacientes que sufrieron una caída tienen una edad media de 77,5 años (DE 11,7), y tuvieron pautados una mediana de 12,5 fármacos (RIC 9,25-15). El 63,6% de las caídas no presentan lesión alguna. Solo se encontró diferencia en cuanto al género en la situación en la que se produce la caída. Conclusiones: Nuestros datos notifican una incidencia de caídas similar a la de centros de nuestro entorno. El perfil del paciente que sufre una caída es el de un hombre mayor, ingresado a cargo de una especialidad médica, con estancias hospitalarias más largas, con alguna comorbilidad y polimedicado, sin una asociación temporal evidente.(AU)

Objective: To estimate the incidence of falls and to know their characteristics in terms of location, temporality and injuries produced, and to analyse the sociodemographic and clinical characteristics of the patients who suffer falls. Methodology: A retrospective observational cohort study was carried out in a level 2 hospital of the Madrid Health Service. Falls in hospitalized patients between July 1, 2018 and June 30, 2019 were studied. The incidence rate of falls per 1,000 days of stay was estimated considering a Poisson distribution. The characteristics of the falls are described: temporality, injuries produced, location of the injuries and prescribed drugs. Sociodemographic and clinical characteristics of patients who suffered a fall were registered. A univariate analysis was performed to compare the results by gender. All data were obtained from the electronic medical record. Results: One hundred and thirty-two falls were studied, which represent a rate of 1.61 falls per 1,000 days of stay. Men, older age, and admission to a medical specialty showed a significantly higher fall rate. The patients who suffered a fall had a mean age of 77.5 years (SD 11.7), and had a median of 12.5 drugs prescribed (IQR: 9.25-15). Of the falls, 63.6% did not present any injury. Difference in gender was only found in the situation in which the fall occurred. Conclusions: Our data report an incidence of falls similar to other institutions in our environment. The profile of the patient who suffers a fall is an older man, admitted under the charge of a medical specialty, with longer hospital stay, with associated comorbidity and polymedicated, without an obvious temporal feature.(AU)

Incidence and characteristics of falls in hospitalized patients: A cohort study.

OBJECTIVE: To estimate the incidence of falls and to know their characteristics in terms of location, temporality and injuries produced, and to analyse the sociodemographic and clinical characteristics of the patients who suffer falls. METHODOLOGY: A retrospective observational cohort study was carried out in a level 2 hospital of the Madrid Health Service. Falls in hospitalized patients between July 1, 2018 and June 30, 2019 were studied. The incidence rate of falls per 1000 days of stay was estimated considering a Poisson distribution. The characteristics of the falls are described: temporality, injuries produced, location of the injuries and prescribed drugs. Sociodemographic and clinical characteristics of patients who suffered a fall were registered. A univariate analysis was performed to compare the results by gender. All data were obtained from the electronic medical record. RESULTS: One hundred and thirty-two falls were studied, which represent a rate of 1.61 falls per 1,000 days of stay. Men, older age, and admission to a medical specialty showed a significantly higher fall rate. The patients who suffered a fall had a mean age of 77.5 years (SD: 11.7), and had a median of 12.5 drugs prescribed (IQR: 9.25-15). Of the falls, 63.6% did not present any injury. Difference in gender was only found in the situation in which the fall occurred. CONCLUSIONS: Our data report an incidence of falls similar to other institutions in our environment. The profile of the patient who suffers a fall is an older man, admitted under the charge of a medical specialty, with longer hospital stay, with associated comorbidity and polymedicated, without an obvious temporal feature.

Annual and perennial Medicago show signatures of parallel adaptation to climate and soil in highly conserved genes.

Human induced environmental change may require rapid adaptation of plant populations and crops, but the genomic basis of environmental adaptation remain poorly understood. We analysed polymorphic loci from the perennial crop Medicago sativa (alfalfa or lucerne) and the annual legume model species M. truncatula to search for a common set of candidate genes that might contribute to adaptation to abiotic stress in both annual and perennial Medicago species. We identified a set of candidate genes of adaptation associated with environmental gradients along the distribution of the two Medicago species. Candidate genes for each species were detected in homologous genomic linkage blocks using genome-environment (GEA) and genome-phenotype association analyses. Hundreds of GEA candidate genes were species-specific, of these, 13.4% (M. sativa) and 24% (M. truncatula) were also significantly associated with phenotypic traits. A set of 168 GEA candidates were shared by both species, which was 25.4% more than expected by chance. When combined, they explained a high proportion of variance for certain phenotypic traits associated with adaptation. Genes with highly conserved functions dominated among the shared candidates and were enriched in gene ontology terms that have shown to play a central role in drought avoidance and tolerance mechanisms by means of cellular shape modifications and other functions associated with cell homeostasis. Our results point to the existence of a molecular basis of adaptation to abiotic stress in Medicago determined by highly conserved genes and gene functions. We discuss these results in light of the recently proposed omnigenic model of complex traits.

Canonical correlations reveal adaptive loci and phenotypic responses to climate in perennial ryegrass.

Germplasm from perennial ryegrass (Lolium perenne L.) natural populations is useful for breeding because of its adaptation to a wide range of climates. Climate-adaptive genes can be detected from associations between genotype, phenotype and climate but an integrated framework for the analysis of these three sources of information is lacking. We used two approaches to identify adaptive loci in perennial ryegrass and their effect on phenotypic traits. First, we combined Genome-Environment Association (GEA) and GWAS analyses. Then, we implemented a new test based on a Canonical Correlation Analysis (CANCOR) to detect adaptive loci. Furthermore, we improved the previous perennial ryegrass gene set by de novo gene prediction and functional annotation of 39,967 genes. GEA-GWAS revealed eight outlier loci associated with both environmental variables and phenotypic traits. CANCOR retrieved 633 outlier loci associated with two climatic gradients, characterized by cold-dry winter versus mild-wet winter and long rainy season versus long summer, and pointed out traits putatively conferring adaptation at the extremes of these gradients. Our CANCOR test also revealed the presence of both polygenic and oligogenic climatic adaptations. Our gene annotation revealed that 374 of the CANCOR outlier loci were positioned within or close to a gene. Co-association networks of outlier loci revealed a potential utility of CANCOR for investigating the interaction of genes involved in polygenic adaptations. The CANCOR test provides an integrated framework to analyse adaptive genomic diversity and phenotypic responses to environmental selection pressures that could be used to facilitate the adaptation of plant species to climate change.

High-Throughput Genome-Wide Genotyping To Optimize the Use of Natural Genetic Resources in the Grassland Species Perennial Ryegrass (Lolium perenne L.).

The natural genetic diversity of agricultural species is an essential genetic resource for breeding programs aiming to improve their ecosystem and production services. A large natural ecotype diversity is usually available for most grassland species. This could be used to recombine natural climatic adaptations and agronomic value to create improved populations of grassland species adapted to future regional climates. However describing natural genetic resources can be long and costly. Molecular markers may provide useful information to help this task. This opportunity was investigated for Lolium perenne L., using a set of 385 accessions from the natural diversity of this species collected right across Europe and provided by genebanks of several countries. For each of these populations, genotyping provided the allele frequencies of 189,781 SNP markers. GWAS were implemented for over 30 agronomic and/or putatively adaptive traits recorded in three climatically contrasted locations (France, Belgium, Germany). Significant associations were detected for hundreds of markers despite a strong confounding effect of the genetic background; most of them pertained to phenology traits. It is likely that genetic variability in these traits has had an important contribution to environmental adaptation and ecotype differentiation. Genomic prediction models calibrated using natural diversity were found to be highly effective to describe natural populations for almost all traits as well as commercial synthetic populations for some important traits such as disease resistance, spring growth or phenological traits. These results will certainly be valuable information to help the use of natural genetic resources of other species.

Evolutionary networks from RADseq loci point to hybrid origins of Medicago carstiensis and Medicago cretacea.

PREMISE: Although hybridization has played an important role in the evolution of many plant species, phylogenetic reconstructions that include hybridizing lineages have been historically constrained by the available models and data. Restriction-site-associated DNA sequencing (RADseq) has been a popular sequencing technique for the reconstruction of hybridization in the next-generation sequencing era. However, the utility of RADseq for the reconstruction of complex evolutionary networks has not been thoroughly investigated. Conflicting phylogenetic relationships in the genus Medicago have been mainly attributed to hybridization, but the specific hybrid origins of taxa have not been yet clarified. METHODS: We obtained new molecular data from diploid species of Medicago section Medicago using single-digest RADseq to reconstruct evolutionary networks from gene trees, an approach that is computationally tractable with data sets that include several species and complex hybridization patterns. RESULTS: Our analyses revealed that assembly filters to exclusively select a small set of loci with high phylogenetic information led to the most-divergent network topologies. Conversely, alternative clustering thresholds or filters on the number of samples per locus had a lower impact on networks. A strong hybridization signal was detected for M. carstiensis and M. cretacea, while signals were less clear for M. rugosa, M. rhodopea, M. suffruticosa, M. marina, M. scutellata, and M. sativa. CONCLUSIONS: Complex network reconstructions from RADseq gene trees were not robust under variations of the assembly parameters and filters. But when the most-divergent networks were discarded, all remaining analyses consistently supported a hybrid origin for M. carstiensis and M. cretacea.

Macroevolutionary dynamics of nectar spurs, a key evolutionary innovation.

Floral nectar spurs are widely considered a key innovation promoting diversification in angiosperms by means of pollinator shifts. We investigated the macroevolutionary dynamics of nectar spurs in the tribe Antirrhineae (Plantaginaceae), which contains 29 genera and 300-400 species (70-80% spurred). The effect of nectar spurs on diversification was tested, with special focus on Linaria, the genus with the highest number of species. We generated the most comprehensive phylogeny of Antirrhineae to date and reconstructed the evolution of nectar spurs. Diversification rate heterogeneity was investigated using trait-dependent and trait-independent methods, and accounting for taxonomic uncertainty. The association between changes in spur length and speciation was examined within Linaria using model testing and ancestral state reconstructions. We inferred four independent acquisitions of nectar spurs. Diversification analyses revealed that nectar spurs are loosely associated with increased diversification rates. Detected rate shifts were delayed by 5-15 Myr with respect to the acquisition of the trait. Active evolution of spur length, fitting a speciational model, was inferred in Linaria, which is consistent with a scenario of pollinator shifts driving diversification. Nectar spurs played a role in diversification of the Antirrhineae, but diversification dynamics can only be fully explained by the complex interaction of multiple biotic and abiotic factors.

Partitioning genetic and species diversity refines our understanding of species-genetic diversity relationships.

Disentangling the origin of species-genetic diversity correlations (SGDCs) is a challenging task that provides insight into the way that neutral and adaptive processes influence diversity at multiple levels. Genetic and species diversity are comprised by components that respond differently to the same ecological processes. Thus, it can be useful to partition species and genetic diversity into their different components to infer the mechanisms behind SGDCs. In this study, we applied such an approach using a high-elevation Andean wetland system, where previous evidence identified neutral processes as major determinants of the strong and positive covariation between plant species richness and AFLP genetic diversity of the common sedge Carex gayana. To tease apart putative neutral and non-neutral genetic variation of C. gayana, we identified loci putatively under selection from a dataset of 1,709 SNPs produced using restriction site-associated DNA sequencing (RAD-seq). Significant and positive relationships between local estimates of genetic and species diversities (α-SGDCs) were only found with the putatively neutral loci datasets and with species richness, confirming that neutral processes were primarily driving the correlations and that the involved processes differentially influenced local species diversity components (i.e., richness and evenness). In contrast, SGDCs based on genetic and community dissimilarities (ß-SGDCs) were only significant with the putative non-neutral datasets. This suggests that selective processes influencing C. gayana genetic diversity were involved in the detected correlations. Together, our results demonstrate that analyzing distinct components of genetic and species diversity simultaneously is useful to determine the mechanisms behind species-genetic diversity relationships.

Long-Term Behaviour of Fly Ash and Slag Cement Grouts for Micropiles Exposed to a Sulphate Aggressive Medium.

Nowadays, one of the most popular ways to get a more sustainable cement industry is using additions as cement replacement. However, there are many civil engineering applications in which the use of sustainable cements is not extended yet, such as special foundations, and particularly micropiles, even though the standards do not restrict the cement type to use. These elements are frequently exposed to the sulphates present in soils. The purpose of this research is to study the effects in the very long-term (until 600 days) of sulphate attack in the microstructure of micropiles grouts, prepared with ordinary Portland cement, fly ash and slag commercial cements, continuing a previous work, in which these effects were studied in the short-term. The microstructure changes have been analysed with the non-destructive impedance spectroscopy technique, mercury intrusion porosimetry and the "Wenner" resistivity test. The mass variation and the compressive strength have also been studied. The impedance spectroscopy has been the most sensitive technique for following the sulphate attack process. Considering the results obtained, micropiles grouts with slag and fly ash, exposed to an aggressive medium with high content of sulphates, have shown good behaviour in the very long-term (600 days) compared to grouts made with OPC.

Influence of Silica Fume Addition in the Long-Term Performance of Sustainable Cement Grouts for Micropiles Exposed to a Sulphate Aggressive Medium.

At present, sustainability is of major importance in the cement industry, and the use of additions such as silica fume as clinker replacement contributes towards that goal. Special foundations, and particularly micropiles, are one of the most suitable areas for the use of sustainable cements. The aim of this research is to analyse the effects in the very long-term (for 600 days) produced by sulphate attack in the microstructure of grouts for micropiles in which OPC (ordinary Portland cement) has been replaced by 5% and 10% silica fume. This line of study is building on a previous work, where these effects were studied in slag and fly ash grouts. Grouts made using a commercial sulphate-resisting Portland cement were also studied. The non-destructive impedance spectroscopy technique, mercury intrusion porosimetry, and Wenner resistivity testing were used. Mass variation and the compressive strength have also been analysed. Apparently, impedance spectroscopy is the most suitable technique for studying sulphate attack development. According to the results obtained, grouts for micropiles with a content of silica fume up to 10% and exposed to an aggressive sulphate medium, have a similar or even better behaviour in the very long-term, compared to grouts prepared using sulphate-resisting Portland cement.

Corolla morphology influences diversification rates in bifid toadflaxes (Linaria sect. Versicolores).

BACKGROUND AND AIMS: The role of flower specialization in plant speciation and evolution remains controversial. In this study the evolution of flower traits restricting access to pollinators was analysed in the bifid toadflaxes (Linaria sect. Versicolores), a monophyletic group of ~30 species and subspecies with highly specialized corollas. METHODS: A time-calibrated phylogeny based on both nuclear and plastid DNA sequences was obtained using a coalescent-based method, and flower morphology was characterized by means of morphometric analyses. Directional trends in flower shape evolution and trait-dependent diversification rates were jointly analysed using recently developed methods, and morphological shifts were reconstructed along the phylogeny. Pollinator surveys were conducted for a representative sample of species. KEY RESULTS: A restrictive character state (narrow corolla tube) was reconstructed in the most recent common ancestor of Linaria sect. Versicolores. After its early loss in the most species-rich clade, this character state has been convergently reacquired in multiple lineages of this clade in recent times, yet it seems to have exerted a negative influence on diversification rates. Comparative analyses and pollinator surveys suggest that the narrow- and broad-tubed flowers are evolutionary optima representing divergent strategies of pollen placement on nectar-feeding insects. CONCLUSIONS: The results confirm that different forms of floral specialization can lead to dissimilar evolutionary success in terms of diversification. It is additionally suggested that opposing individual-level and species-level selection pressures may have driven the evolution of pollinator-restrictive traits in bifid toadflaxes.

Coalescent simulations reveal hybridization and incomplete lineage sorting in Mediterranean Linaria.

We examined the phylogenetic history of Linaria with special emphasis on the Mediterranean sect. Supinae (44 species). We revealed extensive highly supported incongruence among two nuclear (ITS, AGT1) and two plastid regions (rpl32-trnL(UAG), trnS-trnG). Coalescent simulations, a hybrid detection test and species tree inference in *BEAST revealed that incomplete lineage sorting and hybridization may both be responsible for the incongruent pattern observed. Additionally, we present a multilabelled *BEAST species tree as an alternative approach that allows the possibility of observing multiple placements in the species tree for the same taxa. That permitted the incorporation of processes such as hybridization within the tree while not violating the assumptions of the *BEAST model. This methodology is presented as a functional tool to disclose the evolutionary history of species complexes that have experienced both hybridization and incomplete lineage sorting. The drastic climatic events that have occurred in the Mediterranean since the late Miocene, including the Quaternary-type climatic oscillations, may have made both processes highly recurrent in the Mediterranean flora.

The colonization history of Juniperus brevifolia (Cupressaceae) in the Azores Islands.

BACKGROUND: A central aim of island biogeography is to understand the colonization history of insular species using current distributions, fossil records and genetic diversity. Here, we analyze five plastid DNA regions of the endangered Juniperus brevifolia, which is endemic to the Azores archipelago. METHODOLOGY/PRINCIPAL FINDINGS: The phylogeny of the section Juniperus and the phylogeographic analyses of J. brevifolia based on the coalescence theory of allele (plastid) diversity suggest that: (1) a single introduction event likely occurred from Europe; (2) genetic diversification and inter-island dispersal postdated the emergence of the oldest island (Santa Maria, 8.12 Ma); (3) the genetic differentiation found in populations on the islands with higher age and smaller distance to the continent is significantly higher than that on the younger, more remote ones; (4) the high number of haplotypes observed (16), and the widespread distribution of the most frequent and ancestral ones across the archipelago, are indicating early diversification, demographic expansion, and recurrent dispersal. In contrast, restriction of six of the seven derived haplotypes to single islands is construed as reflecting significant isolation time prior to colonization. CONCLUSIONS/SIGNIFICANCE: Our phylogeographic reconstruction points to the sequence of island emergence as the key factor to explain the distribution of plastid DNA variation. The reproductive traits of this juniper species (anemophily, ornithochory, multi-seeded cones), together with its broad ecological range, appear to be largely responsible for recurrent inter-island colonization of ancestral haplotypes. In contrast, certain delay in colonization of new haplotypes may reflect intraspecific habitat competition on islands where this juniper was already present.

Talasemia asociada a embarazo / Thalassemia associated to pregnancy

La Talasemia es un desorden congénito hemolítico causado por una deficiencia parcial o completa de la síntesis de las cadenas alfa o beta de las globinas de la hemoglobina. Se manifiesta en una amplia gama de cuadros clínicos que van desde la muerte intrauterina hasta la microcitosis asintomática sin anemia. El depósito de hierro constituye la complicación más importante de la talasemia y su mayor preocupación en el manejo. Existen escasos reportes de esta condición asociada a embarazo, se sabe poco acerca de su manejo y de las complicaciones que puede tener en el embarazo. Presentamos una paciente portadora de Talasemia, en la cual se manejó su embarazo en nuestro servicio.

Tireoidite de Hashimoto e neoplasma maligno da tireóide / Hashimoto's thyroiditis and malignant neoplasms of the thyroid

A tireoidite de Hashimoto é uma doença tireoidiana comum. Sua associaçao com neoplasmas malignos da tireóide é citada na literatura como de 0,5 a 32 por cento , maior em nódulos frios solitários. A dificuldade em diagnosticar esta associaçao faz com que a conduta diante da tireoidite de Hashimoto seja controversa. Revisamos os dados de 30 doentes com diagnóstico de tireoidite de Hashimoto com nódulos tireoidianos tratados de abril de 1984 a agosto de 1992 no Departamento de Cirurgia da Faculdade de Ciências Médicas da Santa Casa de Sao Paulo. Destes, sete (23,3 por cento ) apresentavam neoplasmas malignos da tireóide, sendo um linfoma (14,3 por cento ), dois carcinomas foliculares (28,6 por cento ) e quatro papilíferos (57,1 por cento ). Com base nestes dados e em outros de literatura, achamos que apesar da tireoidite de Hashimoto ser afecçao de tratamento clínico, todo paciente com este diagnóstico e que apresente na sua evoluçao o aparecimento de nódulo hipo ou normocaptante, deve ser submetido a tratamento cirúrgico