Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus

Adult neurogenesis persists in the hippocampus of most mammal species during postnatal and adult life, including humans, although it declines markedly with age. The mechanisms driving the age-dependent decline of hippocampal neurogenesis are yet not fully understood. The progressive loss of neural stem cells (NSCs) is a main factor, but the true neurogenic output depends initially on the actual number of activated NSCs in each given time point. Because the fraction of activated NSCs remains constant relative to the total population, the real number of activated NSCs declines in parallel to the total NSC pool. We investigated aging-associated changes in NSCs and found that there are at least two distinct populations of NSCs. An alpha type, which maintains the classic type-1 radial morphology and accounts for most of the overall NSC mitotic activity; and an omega type characterized by increased reactive-like morphological complexity and much lower probability of division even under a pro-activation challenge. Finally, our results suggest that alpha-type NSCs are able to transform into omega-type cells overtime and that this phenotypic and functional change might be facilitated by the chronic inflammation associated with aging.PI-2016-0011/Eusko Jaurlaritza/International BFU2015-66689/Ministerio de Economía y Competitividad/International RyC-2012-11137/Ministerio de Economía y Competitividad/International SAF-2015-70866/Ministerio de Economía y Competitividad/Internationa

Holm oak decline is determined by shifts in fine root phenotypic plasticity in response to belowground stress

Climate change and pathogen outbreaks are the two major causes of decline in Mediterranean holm oak trees (Quercus ilex L. subsp. ballota (Desf.) Samp.). Crown-level changes in response to these stressful conditions have been widely documented but the responses of the root systems remain unexplored. The effects of environmental stress over roots and its potential role during the declining process need to be evaluated. We aimed to study how key morphological and architectural root parameters and nonstructural carbohydrates of roots are affected along a holm oak health gradient (i.e. within healthy, susceptible and declining trees). Holm oaks with different health statuses had different soil resource-uptake strategies. While healthy and susceptible trees showed a conservative resource-uptake strategy independently of soil nutrient availability, declining trees optimized soil resource acquisition by increasing the phenotypic plasticity of their fine root system. This increase in fine root phenotypic plasticity in declining holm oaks represents an energy-consuming strategy promoted to cope with the stress and at the expense of foliage maintenance. Our study describes a potential feedback loop resulting from strong unprecedented belowground stress that ultimately may lead to poor adaptation and tree death in the Spanish dehesa.This research was mainly funded by the Spanish Government through the IBERYCA project (CGL2017-84723-P), its associated FPI scholarship BES-2014-067971 (ME-V) and SMARTSOIL (PID2020-113244GB-C21). It was further supported by the BC3 María de Maeztu excellence accreditation (MDM-2017-0714; the Spanish Government) and by the BERC 2018–2021 and the UPV/EHU-GV IT-1018-16 programme (Basque Government). Additionally, this research was further supported through the ‘Juan de la Cierva programme’ (MV; IJCI-2017-34640; the Spanish Government) and one project funded by the Romanian Ministry of Research, Innovation and Digitization through UEFISCDI (A-MH; REASONING, PN-III-P1-1.1-TE-2019-1099)

Evolución de Studium. Despliegue de la plataforma moodle 2.x

Memoria ID-2012.001. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2012-2013

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Holm oak decline in human-shaped savannahs: Physiological and ecological basis

229 p.Holm oak decline in Iberian dehesas, characterized by defoliation, is caused by the interaction of multiple stressors such as climate change-related events, invasive pathogens, and changes in dehesa use and management. Understanding the biochemical and physiological mechanisms preceding and following defoliation remains a challenge. This dissertation conducted a regional study across nine dehesa sites, examining physiological, morphological, and ecological responses underlying holm oak decline. Findings highlighted the oak's ability to acclimate through adjustments in photoprotective compounds. Defoliation occurred when stress exceeded certain physiological threshold. This was accompanied by a shift in energy allocation towards soil resource acquisition through fine root phenotypic plasticity. The loss of tree health was related to upregulated biogeochemical steps and the subsequent downregulation of soil nutrients, forming a tree-soil feedback loop. This research deepens our understanding of holm oak decline, including factors defining tree health, underlying mechanisms, and tree-soil interactions, offering insights to predict, prevent, and mitigate this decline in Iberian dehesa.bc3: Basque Center for Climate Chang

Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus

Adult neurogenesis persists in the hippocampus of most mammal species during postnatal and adult life, including humans, although it declines markedly with age. The mechanisms driving the age-dependent decline of hippocampal neurogenesis are yet not fully understood. The progressive loss of neural stem cells (NSCs) is a main factor, but the true neurogenic output depends initially on the actual number of activated NSCs in each given time point. Because the fraction of activated NSCs remains constant relative to the total population, the real number of activated NSCs declines in parallel to the total NSC pool. We investigated aging-associated changes in NSCs and found that there are at least two distinct populations of NSCs. An alpha type, which maintains the classic type-1 radial morphology and accounts for most of the overall NSC mitotic activity; and an omega type characterized by increased reactive-like morphological complexity and much lower probability of division even under a pro-activation challenge. Finally, our results suggest that alpha-type NSCs are able to transform into omega-type cells overtime and that this phenotypic and functional change might be facilitated by the chronic inflammation associated with aging.Eusko Jaurlaritza, Grant/Award Number: PI-2016-0011; Ministerio de Economia y Competitividad, Grant/Award Number: BFU2015-66689, RyC-2012-11137 and SAF-2015-7086

Greater phylogenetic distance from native oaks predicts escape from insect leaf herbivores by non-native oak saplings.

Premise Non-native plant species have been hypothesized to experience lower herbivory in novel environments as a function of their phylogenetic distance from native plant species. Although recent work has found support for this prediction, the plant traits responsible for such patterns have been largely overlooked. Methods In a common garden experiment in northwestern Spain, we tested whether oak species (Quercus spp.) not native to this region that are phylogenetically more distantly related to native species exhibit less insect leaf herbivory. In addition, we also investigated plant traits potentially correlated with any such effect of phylogenetic distance. Results As expected, phylogenetic distance from native species negatively predicted insect leaf herbivory on non-native oaks. In addition, we found that the leaf traits, namely phosphorus and condensed tannins, were significantly associated with herbivory, suggesting that they are associated with the effect of phylogenetic distance on leaf herbivory on non-native oak species. Conclusions This study contributes to a better understanding of how evolutionary relationships (relatedness) between native and non-native plant species determine the latter's success in novel environments via locally shared enemies, and encourages more work investigating the plant traits that mediate the effects of phylogenetic distance on enemy escape

Biogeochemical cycles in holm oak dehesas

<p><span>In anthropic savannah ecosystems from the Iberian Peninsula (i.e., dehesa), complex interactions between climate change, pathogen outbreaks and human land use are presumed to be behind the observed increase in holm oak decline. These environmental disturbances alter the plant-soil microbial continuum, which can destabilize the ecological balance that sustains tree health. Yet, little is known about the underlying mechanisms, particularly the directions and nature of the causal-effect relations between plants and soil microbial communities. </span></p> <p><span>In this study, we aimed to determine the role of plant-soil feedbacks in climate-induced holm oak decline in the Iberian dehesa. Using a gradient of holm oak health, we reconstructed key soil biogeochemical cycles mediated by soil microbial communities. We used quantitative microbial element cycling (QMEC), a functional gene-array-based high-throughput technique to assess microbial functional potential in carbon (C), nitrogen (N), phosphorous (P), and sulfur (S) cycling. </span></p> <p><span>The onset of holm oak decline was positively related with the increase in relative abundance of soil microbial functional genes associated with denitrification and phosphorous mineralization (i.e., <em>nirS3</em>, <em>ppx</em> and <em>pqqC</em>; parameter value: 0.21, 0.23 and 0.4; p<0.05). The structural equation model (ꭓ<sup>2</sup> = 32.26, p-value = 0.73), moreover, showed a negative association between these functional genes and soil nutrient availability (i.e., mainly mineral nitrogen and phosphate). Particularly, the holm oak crown health was mainly determined by the abundance of phosphate (parameter value=0.27; p-value<0.05) and organic phosphorus (parameter value=-0.37; p-value<0.5). </span></p> <div> <p><span>Hence, we propose a potential tree-soil feedback loop, in which the decline of holm oak promotes changes in the soil environment that trigger changes in key microbial-mediated metabolic pathways related to the net loss of soil N and P mineral forms. The shortage of essential nutrients, in turn, affects the ability of the trees to withstand the environmental stressors to which they are exposed. </span></p> </div><p>Funding provided by: Government of Spain<br>Crossref Funder Registry ID: https://ror.org/038jjxj40<br>Award Number: CGL2017-84723-P</p><p>Funding provided by: Ministerio de Ciencia e Innovación<br>Crossref Funder Registry ID: https://ror.org/05r0vyz12<br>Award Number: BES- 2014-067971</p><p>Funding provided by: Ministerio de Ciencia e Innovación<br>Crossref Funder Registry ID: https://ror.org/05r0vyz12<br>Award Number: PID2020-113244GB-C21</p><p>Funding provided by: Ministerio de Ciencia e Innovación<br>Crossref Funder Registry ID: https://ror.org/05r0vyz12<br>Award Number: PID2020-113244GA-C22</p><p>Funding provided by: Basque Centre for Climate Change<br>Crossref Funder Registry ID: https://ror.org/00eqwze33<br>Award Number: MDM-2017-0714</p><p>Funding provided by: Basque Government<br>Crossref Funder Registry ID: https://ror.org/00pz2fp31<br>Award Number: UPV/EHU- GV IT-1648-22</p><p>Funding provided by: Ministerio de Ciencia e Innovación<br>Crossref Funder Registry ID: https://ror.org/05r0vyz12<br>Award Number: IJCI-2017-34640</p><p>Funding provided by: European Union<br>Crossref Funder Registry ID: https://ror.org/019w4f821<br>Award Number: 101000289</p><p>These data have been collected in holm oak dehesas. <span>To account for the soil spatial heterogeneity, three different soil samples were collected below each of the 162 holm oak trees at a distance of 1 m from each trunk. The depth at which we collected the soil was determined by the depth where the shallowest holm oak fine root density peak was located. As we collected both the soil and the roots at the same depth, and this holm oak root depth was affected by the presence of the herbaceous root layer and historical land management practices, we excavated until we reached the soil layer predominantly containing holm oak roots. This typically occurred at an average depth of 15 cm and generally did not exceed 30 cm. Then, the three soil subsamples were pooled in one single composite sample that was maintained at 4°C (12h) until processing in the laboratory. These soil samples were then used to do soil chemical analyses and to quantify soil microbial functional genes. Specifically, for the soil chemical analyses, the 162 soil samples were dried at room temperature (~20ºC), sieved using a 2-mm mesh size and stored in darkness (cf. section 2.4.). Regarding the analysis of soil microbial functional genes, aliquots from the 162 soil samples were frozen at -20ºC just upon arrival at the laboratory every day after sampling and stored in darkness for approximately one month after sampling, until DNA extraction (cf. section 2.5.). </span></p&gt