Search

[Background] Intramuscular fat (IMF) content and its fatty acid (FA) composition are typically controlled by several genes, each with a small effect. In the current study, to pinpoint candidate genes and putative regulators involved in FA composition, we performed a multivariate integrative analysis between intramuscular FA and transcriptome profiles of porcine longissimus dorsi (LD) muscle. We also carried out a combination of network, regulatory impact factor (RIF), in silico prediction of putative target genes, and functional analyses to better support the biological relevance of our findings., [Results] For this purpose, we used LD RNA-Seq and intramuscular FA composition profiles of 129 Iberian × Duroc backcrossed pigs. We identified 378 correlated variables (13 FA and 365 genes), including six FA (C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, C18:0, and C16:1n-7) that were among the most interconnected variables in the predicted network. The detected FA-correlated genes include genes involved in lipid and/or carbohydrate metabolism or in regulation of IMF deposition (e.g., ADIPOQ, CHUK, CYCS, CYP4B1, DLD, ELOVL6, FBP1, G0S2, GCLC, HMGCR, IDH3A, LEP, LGALS12, LPIN1, PLIN1, PNPLA8, PPP1R1B, SDR16C5, SFRP5, SOD3, SNW1, and TFRC), meat quality (GALNT15, GOT1, MDH1, NEU3, PDHA1, SDHD, and UNC93A), and transport (e.g., EXOC7 and SLC44A2). Functional analysis highlighted 54 over-represented gene ontology terms, including well-known biological processes and pathways that regulate lipid and carbohydrate metabolism. RIF analysis suggested a pivotal role for six transcription factors (CARHSP1, LBX1, MAFA, PAX7, SIX5, and TADA2A) as putative regulators of gene expression and intramuscular FA composition. Based on in silico prediction, we identified putative target genes for these six regulators. Among these, TADA2A and CARHSP1 had extreme RIF scores and present novel regulators in pigs. In addition, the expression of TADA2A correlated (either positively or negatively) with C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, and that of CARHSP1 correlated (positively) with the C16:1n-7 lipokine. We also found that these two transcription factors share target genes that are involved in lipid metabolism (e.g., GOT1, PLIN1, and TFRC)., [Conclusions] This integrative analysis of muscle transcriptome and intramuscular FA profile revealed valuable information about key candidate genes and potential regulators for FA and lipid metabolism in pigs, among which some transcription factors are proposed to control gene expression and modulate FA composition differences.

[ES] The intensification of agriculture is impacting farmland and is recognised as a main driver for biodiversity loss in these environments. Many farmland bird populations have been declining in recent decades because of agricultural intensification. This is the case of the Red-legged Partridge Alectoris rufa, a game bird that inhabits farming landscapes and has recently suffered drastic population declines in Spain. To fully understand the effects that agricultural intensification has on these birds, it is crucial to deepen the knowledge regarding their feeding habits and how these may vary seasonally. The aim of this study was to provide a detailed and reliable description of wild partridges’ plant diet composition. For this purpose, we collected faecal samples from 35 partridge flocks during autumn, winter and spring, and used DNA metabarcoding to identify plants consumed by this species. We used nuclear and chloroplastic barcodes for the amplification of ITS2 and rbcL gene regions, respectively. Our results showed that the diet of partridges was highly diverse, mainly consisting of cereals, weeds and legumes. The most frequently consumed genus was Hordeum, followed by Lolium, Papaver, Medicago and Avena. We further showed that diet composition varied significantly amongst seasons, with a higher proportion of cultivated plants (> 25%) being consumed during autumn and winter. During the cereal sowing period, cropped plants might be consumed as sown seeds, which are often coated with pesticides and could represent an important risk. In spring, before breeding, the diet was mostly composed of weeds. Plants of the Papaver genus could be consumed for anti-parasitic purposes, and as a source of antioxidants and carotenoids to increase ornamental coloration, especially during pairing and laying. Our results highlight the importance of maintaining heterogenous farming landscapes with fallow lands and field margins as sources of weeds to help the conservation of this spe, [DE] Die Intensivierung der Landwirtschaft hat Auswirkungen auf die landwirtschaftlich genutzten Flächen und gilt als Hauptursache für den Rückgang der biologischen Vielfalt in diesen Lebensräumen. Viele Vogelpopulationen in ländlichen Gegenden sind in den letzten Jahrzehnten aufgrund der Intensivierung der Landwirtschaft geschrumpft. Das trifft für das Rothuhn Alectoris rufa, zu, einem Wildvogel, der in Agrarlandschaften lebt und in letzter Zeit in Spanien einen drastischen Bestandsrückgang erlebt hat. Um die Auswirkungen der Intensivierung der Landwirtschaft auf diese Vögel vollständig zu verstehen, ist es entscheidend wichtig, mehr über ihre Ernährungsgewohnheiten und ihre jahreszeitlichen Schwankungen herauszufinden. Ziel dieser Studie war die Erstellung einer detaillierten und belastbaren Beschreibung der pflanzlichen Nahrungszusammensetzung von Rothühnern. Hierfür sammelten wir im Herbst, Winter und Frühjahr Kotproben von 35 Rothuhngruppen und identifizierten mit Hilfe von DNA-Metabarcoding die von ihnen gefressenen Pflanzen. Für die Amplifizierung der ITS2- bzw. rbcL-Genregionen setzten wir Barcodes von Zellkernen und Chloroplasten ein. Unsere Ergebnisse zeigen, dass die Ernährung der Rothühner sehr vielfältig ist und hauptsächlich aus Getreide, Unkräutern und Hülsenfrüchten besteht. Die am häufigsten gefressene Gattung war Hordeum, gefolgt von Lolium, Papaver, Medicago und Avena. Wir konnten außerdem zeigen, dass die Zusammensetzung der Nahrung je nach Jahreszeit erheblich variiert, wobei im Herbst und Winter ein höherer Anteil an Kulturpflanzen (> 25%) verzehrt wird. Während der Getreideaussaat wurden die geernteten Pflanzen vermutlich als Saatgut verzehrt, das wegen seiner häufigen Pestizid-Belastung ein erhebliches Risiko darstellen könnte. Im Frühjahr, vor der Paarung, bestand die Nahrung hauptsächlich aus Kräutern. Pflanzen der Gattung Papaver werden möglicherweise zur Bekämpfung von Parasiten und als Quelle von Antioxidantien und Carotinoiden für die S

Interactions with angiosperms have been hypothesised to play a crucial role in driving diversification among insects, with a particular emphasis on pollinator insects. However, support for coevolutionary diversification in insect¿plant interactions is weak. Macroevolutionary studies of insect and plant diversities support the hypothesis that angiosperms diversified after a peak in insect diversity in the Early Cretaceous. Here, we used the family-level fossil record of insects as a whole, and insect pollinator families in particular, to estimate diversification rates and the role of angiosperms on insect macroevolutionary history using a Bayesian process-based approach. We found that angiosperms played a dual role that changed through time, mitigating insect extinction in the Cretaceous and promoting insect origination in the Cenozoic, which is also recovered for insect pollinator families only. Although insects pollinated gymnosperms before the angiosperm radiation, a radiation of new pollinator lineages began as angiosperm lineages increased, particularly significant after 50¿Ma. We also found that global temperature, increases in insect diversity, and spore plants were strongly correlated with origination and extinction rates, suggesting that multiple drivers influenced insect diversification and arguing for the investigation of different explanatory variables in further studies.

The tropical seagrass Halophila stipulacea invaded the Eastern Mediterranean Sea in the late nineteenth century and progressively spread throughout the basin ever since. Its spread is expected to continue north-westward as the Mediterranean Sea becomes warmer, potentially changing the seagrass biogeography of the basin. Given the power of genomics to assess invasion dynamics in non-model species, we report the first ddRAD-seq study of H. stipulacea and small-scale population genomic analysis addressing its century-old Mediterranean invasion. Based on 868 SNPs and 35 genotyped native (Red Sea) and exotic (from Cyprus, Greece, and Italy) samples, results suggest that genetic structure was high, especially between major geographic discontinuities, and that exotic populations maintain comparably lower genetic diversity than native populations, despite 130 years of invasion. The evidence of high heterozygosity excess, coupled with previously reported male-dominated and rare flowering records in the exotic range, suggests that clonal propagation likely played a pivotal role in the successful colonization and spread of H. stipulacea in the Mediterranean. This shift in reproductive strategy, particularly evident in the Italian populations located closest to the western boundary and representing more recent establishments, underscores the importance of this cost-effective mode of reproduction, especially during the initial stages of invasion, raising questions about the species future expansion trajectory. Our findings serve as a catalyst for future research into the species’ invasion dynamics, including deciphering the intricate roles of acclimatization and rapid adaptation, important for a comprehensive assessment of invasion risks and improving management strategies aimed at conserving seagrass ecosystems.

Liquid-phase transmission electron microscopy is a burgeoning experimental technique for monitoring nanoscale dynamics in a liquid environment, increasingly employing microfluidic reactors to control the composition of the sample solution. Current challenges comprise fast mass transport dynamics inside the central nanochannel of the liquid cell, typically flow cells, and reliable fixation of the specimen in the limited imaging area. In this work, we present a liquid cell concept – the diffusion cell – that satisfies these seemingly contradictory requirements by providing additional on-chip bypasses to allow high convective transport around the nanochannel in which diffusive transport predominates. Diffusion cell prototypes are developed using numerical mass transport models and fabricated on the basis of existing two-chip setups. Important hydrodynamic parameters, i.e., the total flow resistance, the flow velocity in the imaging area, and the time constants of mixing, are improved by 2-3 orders of magnitude compared to existing setups. The solution replacement dynamics achieved within seconds already match the mixing timescales of many ex-situ scenarios, and further improvements are possible. Diffusion cells can be easily integrated into existing liquid-phase transmission electron microscopy workflows, provide correlation of results with ex-situ experiments, and can create additional research directions addressing fast nanoscale processes.

In the last few decades, there has been a growing interest in understanding the behavior of personal care products (PCPs) in the aquatic environment. In this regard, the aim of this study is to estimate the accumulation and effects of four PCPs within the clam Ruditapes philippinarum. The PCPs selected were triclosan, OTNE, benzophenone-3, and octocrylene. A progressive uptake was observed and maximum concentrations in tissues were reached at the end of the exposure phase, up to levels of 0.68 µg g−1, 24 µg g−1, 0.81 µg g−1, and 1.52 µg g−1 for OTNE, BP-3, OC, and TCS, respectively. After the PCP post-exposure period, the removal percentages were higher than 65%. The estimated logarithm bioconcentration factor ranged from 3.34 to 2.93, in concordance with the lipophobicity of each substance. No lethal effects were found although significant changes were observed for ethoxyresorufin O-demethylase activity, glutathione S-transferase activity, lipid peroxidation, and DNA damage.

In the Anthropocene, many species are rapidly shifting their ranges in response to human-driven habitat modifications. Studying patterns and genetic signatures of range shifts helps to understand how species cope with environmental disturbances and predict future shifts in the face of global environmental change. We investigated the genetic signature of a contemporary wide-range expansion observed in the Iberian common vole Microtus arvalis asturianus shortly after a colonization event. We used mtDNA and microsatellite data to investigate patterns of genetic diversity, structure, demography, and gene flow across 57 localities covering the historical range of the species and the newly colonized area. The results showed a genetic footprint more compatible with a true range expansion (i.e. the colonization of previously unoccupied areas), than with a model of “colonization from within” (i.e. local expansions from small, unnoticed populations). Genetic diversity measures indicated that the source population was likely located at the NE of the historical range, with a declining gradient of genetic diversity towards the more recently invaded areas. At the expansion front, we observed the greatest gene flow and smallest pairwise differences between nearby localities. Both natural landscape features (rivers) and recent anthropogenic barriers (roads, railways) explained a large proportion of genetic variance among populations and had a significant impact on the colonization pathways used by voles.

Vaccines are the most effective preventive intervention to reduce the impact of infectious diseases worldwide. In particular, tick-borne diseases represent a growing burden for human and animal health worldwide and vaccines are the most effective and environmentally sound approach for the control of vector infestations and pathogen transmission. However, the development of effective vaccines for the control of tick-borne diseases with combined vector-derived and pathogen-derived antigens is one of the limitations for the development of effective vaccine formulations. Quantum biology arise from findings suggesting that living cells operate under non-trivial features of quantum mechanics, which has been proposed to be involved in DNA mutation biological process. Then, the electronic structure of the molecular interactions behind peptide immunogenicity led to quantum immunology and based on the definition of the photon as a quantum of light, the immune protective epitopes were proposed as the immunological quantum. Recently, a quantum vaccinomics approach was proposed based on the characterization of the immunological quantum to further advance the design of more effective and safe vaccines. In this chapter, we describe methods of the quantum vaccinomics approach based on proteins with key functions in cell interactome and regulome of vector–host–pathogen interactions for the identification by yeast two-hybrid screen and the characterization by in vitro protein–protein interactions and musical scores of protein interacting domains, and the characterization of conserved protective epitopes in protein interacting domains. These results can then be used for the design and production of chimeric protective antigens.

Predicting the regional net greenhouse gas emissions (Net GHG) of grasslands is increasingly important, as these are one of the most globally widespread vegetation types, providing several ecosystem services. In this study, we assessed the regional soil organic carbon (SOC) change over a 30-year period (1981–2010), and the annual GHG balance for 405,000 ha of moist temperate Spanish grassland associated with dairy cow production. To do this we used the following: (i) an integrated modelling framework comprising geographic information systems (GIS); (ii) the RothC model to simulate SOC changes in managed grasslands under moist temperate conditions; and (iii) Tier 2 recent IPCC methods to estimate emissions. The results showed an average regional SOC change rate of 0.16 Mg C ha−1 year−1, associated with the initial SOC and livestock density. The annual GHG balance was positive, contributing to global warming by 5.6 Mg CO2-e ha−1 year−1. Livestock density was the main factor affecting net GHG emissions in the grasslands associated with dairy production in northern Spain. We determined a livestock density threshold of 0.95 LU ha−1, below which there is no SOC accumulation, and a threshold of approximately 0.4 LU ha−1, above which net GHG per livestock unit (LU) are reduced. In conclusion, our study confirms the importance of dairy cow grazing systems in preserving and/or enhancing SOC stocks in the grasslands of northern Spain. It is therefore crucial to optimise the livestock density considering large variety of feed intake and alternative manure management mitigation options to reduce the net GHG emissions.

Two cellulose nanocrystals/single-walled carbon nanotube (CNC/SW) hybrids, using two cellulose polymorphs, were evaluated as electrochemical transducers: CNC type I (CNC-I/SW) and CNC type II (CNC-II/SW). They were synthesized and fully characterized, and their analytical performance as electrochemical sensors was carefully studied. In comparison with SWCNT-based and screen-printed carbon electrodes, CNC/SW sensors showed superior electroanalytical performance in terms of sensitivity and selectivity, not only in the detection of small metabolites (uric acid, dopamine, and tyrosine) but also in the detection of complex glycoproteins (alpha-1-acid glycoprotein (AGP)). More importantly, CNC-II/SW exhibited 20 times higher sensitivity than CNC-I/SW for AGP determination, yielding a LOD of 7 mg L−1.These results demonstrate the critical role played by nanocellulose polymorphism in the electrochemical performance of CNC/SW hybrid materials, opening new directions in the electrochemical sensing of these complex molecules. In general, these high-active-surface hybrids smartly exploited the preserved non-oxidized SW conductivity with the high aqueous dispersibility of the CNC, avoiding the use of organic solvents or the incorporation of toxic surfactants during their processing, making the CNC/SW hybrids promising nanomaterials for electrochemical detection following greener approaches.

Pennatulaceans (Octocorallia: Pennatulacea) are among the most dominant octocoral species living in soft bottom communities. Some of them are cosmopolitan and have been recorded in all seas and oceans of the world, from shallow waters up to about 6260 m deep. In the present study, we try to find answers to questions about the biogeographical distribution of sea pens including most recently described species. We also evaluate the diversity and faunistic affinities among pennatulaceans of the world’s oceans, and determine the degree of faunistic isolation of the Mediterranean Sea from the Atlantic. Finally, we return to the old debate about the hypothetical oldest diversification center of sea pen lineages.

Tumour progression and therapy tolerance are highly regulated and complex processes largely dependent on the plasticity of cancer cells and their capacity to respond to stress. The higher plasticity of cancer cells highlights the need for identifying targetable molecular pathways that challenge cancer cell survival. Here, we show that N7-guanosine methylation (m7G) of tRNAs, mediated by METTL1, regulates survival to stress conditions in cancer cells. Mechanistically, we find that m7G in tRNAs protects them from stress-induced cleavage and processing into 5’ tRNA fragments. Our analyses reveal that the loss of tRNA m7G methylation activates stress response pathways, sensitising cancer cells to stress. Furthermore, we find that the loss of METTL1 reduces tumour growth and increases cytotoxic stress in vivo. Our study uncovers the role of m7G methylation of tRNAs in stress responses and highlights the potential of targeting METTL1 to sensitise cancer cells to chemotherapy.

This article examines the origins of the shorter commutes typically observed for women, a phenomenon that contributes to the poorer work outcomes they typically suffer. The analysis extends previous research on the gender gap in commuting by using econometric decomposition techniques that are novel in this field which, combined with a Spanish nationally representative survey that allows for an exhaustive control of the different elements identified in the literature as possible determinants of gender differences in commuting to work, allows quantifying the specific influence of a wide range of individual, family, territorial and work-related elements. The evidence obtained shows that the gender gap in commuting is not the result of the relative characteristics of women, but of the presence of a systematic pattern of lower mobility that emerges when women are compared with observationally similar men. Yet, this pattern of lower mobility is not observed for certain groups of women whose behavior in the labor market is generally more egalitarian, such as women with higher education, without family responsibilities or without a partner, which is consistent with the presence of cultural or social constraints that tend to limit women’s mobility.

NASA’s Perseverance rover’s Mars Environmental Dynamics Analyzer is collecting data at Jezero crater, characterizing the physical processes in the lowest layer of the Martian atmosphere. Here we present measurements from the instrument’s first 250 sols of operation, revealing a spatially and temporally variable meteorology at Jezero. We find that temperature measurements at four heights capture the response of the atmospheric surface layer to multiple phenomena. We observe the transition from a stable night-time thermal inversion to a daytime, highly turbulent convective regime, with large vertical thermal gradients. Measurement of multiple daily optical depths suggests aerosol concentrations are higher in the morning than in the afternoon. Measured wind patterns are driven mainly by local topography, with a small contribution from regional winds. Daily and seasonal variability of relative humidity shows a complex hydrologic cycle. These observations suggest that changes in some local surface properties, such as surface albedo and thermal inertia, play an influential role. On a larger scale, surface pressure measurements show typical signatures of gravity waves and baroclinic eddies in a part of the seasonal cycle previously characterized as low wave activity. These observations, both combined and simultaneous, unveil the diversity of processes driving change on today’s Martian surface at Jezero crater.

Salinity is one of the most constraining environmental factors that limits plant growth and productivity because it disturbs mineral nutrition by triggering interactions at the interface soil roots. It implies a notable competition between sodium (Na) and potassium (K), with this last mineral being a key nutrient for plants. Using the halophyte Cakile maritima as a model plant grown in hydroponic conditions, this study was aimed to analyze how the simultaneous stressful conditions of high salinity (400 mM NaCl) and K deficiency (0 mM) for 15 days affect plant growth, ion balance, and antioxidant and NADPH-generating systems. Among the parameters analyzed, the most remarkable changes were observed in leaves, with drastic increases in the Na/K, Na/Ca and Na/Mg ratios, an enhanced accumulation of anthocyanins, and the induction of 3 new copper/zinc superoxide dismutase (CuZnSOD) isozymes in plants simultaneously exposed to both stresses. Taken together, the data revealed that the combination of both, high salinity and K deficiency, caused oxidative stress and modulated the whole antioxidative response of C. maritima in leaves and roots. Besides the differential response underwent by both organs, considering the different parameters analyzed under these stressful conditions, the most notable traits were that the effect of both stresses seems to be not additive and that salinity appears to improve C. maritima response to K, a behavior not manifested in glycophyte species. Taken together our data support that, under extreme conditions that lead to an excess of ROS production, the induction of several CuZn-SODs in C. maritima may be one of the most outstanding strategies for the adaptation of this plant species to survive.

Future gravitational wave interferometers such as the Laser Interferometer Space Antenna, Taiji, DECi-hertz Interferometer Gravitational wave Observatory and TianQin will enable precision studies of the environment surrounding black holes. These detectors will probe the millihertz frequency range, as yet unexplored by current gravitational wave detectors. Furthermore, sources will remain in band for durations of up to years, meaning that the inspiral phase of the gravitational wave signal, which can be affected by the environment, will be observable. In this paper, we study intermediate and extreme mass ratio binary black hole inspirals, and consider three possible environments surrounding the primary black hole: accretion disks, dark matter spikes and clouds of ultra-light scalar fields, also known as gravitational atoms. We present a Bayesian analysis of the detectability and measurability of these three environments. Focusing for concreteness on the case of a detection with LISA, we show that the characteristic imprint they leave on the gravitational waveform would allow us to identify the environment that generated the signal and to accurately reconstruct its model parameters.

[Background]: Lake Baikal, the world’s deepest freshwater lake, contains important numbers of Candidatus Patescibacteria (formerly CPR) in its deepest reaches. However, previously obtained CPR metagenome-assembled genomes recruited very poorly indicating the potential of other groups being present. Here, we have applied for the first time a long-read (PacBio CCS) metagenomic approach to analyze in depth the Ca. Patescibacteria living in the bathypelagic water column of Lake Baikal at 1600 m. [Results]: The retrieval of nearly complete 16S rRNA genes before assembly has allowed us to detect the presence of a novel and a likely endemic group of Ca. Patescibacteria inhabiting bathypelagic Lake Baikal. This novel group seems to possess extremely high intra-clade diversity, precluding complete genomes' assembly. However, read binning and scaffolding indicate that these microbes are similar to other Ca. Patescibacteria (i.e. parasites or symbionts), although they seem to carry more anabolic pathways, likely reflecting the extremely oligotrophic habitat they inhabit. The novel bins have not been found anywhere, but one of the groups appears in small amounts in an oligotrophic and deep alpine Lake Thun. We propose this novel group be named Baikalibacteria. [Conclusion]: The recovery of 16S rRNA genes via long-read metagenomics plus the use of long-read binning to uncover highly diverse “hidden” groups of prokaryotes are key strategies to move forward in ecogenomic microbiology. The novel group possesses enormous intraclade diversity akin to what happens with Ca. Patescibacteria at the interclade level, which is remarkable in an environment that has changed little in the last 25 million years.

Obesity is associated with adipose tissue dysfunction through the differentiation and expansion of pre-adipocytes to adipocytes (hyperplasia) and/or increases in size of pre-existing adipocytes (hypertrophy). A cascade of transcriptional events coordinates the differentiation of pre-adipocytes into fully differentiated adipocytes; the process of adipogenesis. Although nicotinamide N-methyltransferase (NNMT) has been associated with obesity, how NNMT is regulated during adipogenesis, and the underlying regulatory mechanisms, remain undefined. In present study we used genetic and pharmacological approaches to elucidate the molecular signals driving NNMT activation and its role during adipogenesis. Firstly, we demonstrated that during the early phase of adipocyte differentiation NNMT is transactivated by CCAAT/Enhancer Binding Protein beta (CEBPB) in response to glucocorticoid (GC) induction. We found that Nnmt knockout, using CRISPR/Cas9 approach, impaired terminal adipogenesis by influencing the timing of cellular commitment and cell cycle exit during mitotic clonal expansion, as demonstrated by cell cycle analysis and RNA sequencing experiments. Biochemical and computational methods showed that a novel small molecule, called CC-410, stably binds to and highly specifically inhibits NNMT. CC-410 was, therefore, used to modulate protein activity during pre-adipocyte differentiation stages, demonstrating that, in line with the genetic approach, chemical inhibition of NNMT at the early stages of adipogenesis impairs terminal differentiation by deregulating the GC network. These congruent results conclusively demonstrate that NNMT is a key component of the GC-CEBP axis during the early stages of adipogenesis and could be a potential therapeutic target for both early-onset obesity and glucocorticoid-induced obesity.

Previous works developed by our research group have shown that the Jurassic rocks of the Central high Atlas (CHA) have recorded a Cretaceous widespread remagnetization. In this chapter, a high resolution paleomagnetic study on 424 new paleomagnetic sites in Mesozoic units of CHA is presented. This work provides new information about the Cretaceous magnetic overprint of the CHA, as well as contributes to the knowledge of the geodynamic evolution of the Atlas. The new results confirm the extent of remagnetization throughout the study area (10,000 km2) in both carbonates (carried by magnetite) and red beds (carried by hematite) showing systematically normal polarity and an inter-folding acquisition. By using small circle techniques, the remagnetization direction (n = 531, Dec = 335.4°, Inc = 42.7° for carbonates and n = 62, Dec = 344.4°, Inc = 41.7° for red beds) and the age of acquisition (100 Ma ± 5 Ma for limestones) have been determined. The remagnetization properties in the carbonates and their paleomagnetic direction are maintained throughout the studied area and the different stratigraphic units. The small but statistically significant difference between the directions of remagnetization in carbonates and red beds suggests a delay in the acquisition in red beds. Remagnetization directions have been restored using small circle techniques, allowing to generate a set of 593 paleo-dips of the beds at 100 Ma. This valuable information has been used in Chap. “ Kinematics of Structures and Basin Evolution in the Central High Atlas. Constraints from AMS and Paleomagnetic Data ” to elaborate palinspastic reconstructions and to study the evolution of the different structures of the CHA. For this purpose, a new diagram (paleo-dip evolution diagram, PED) is here proposed.

Sepsis is a syndromic response to infection and is frequently a final common pathway to death from many infectious diseases worldwide. The complexity and high heterogeneity of sepsis hinder the possibility to treat all patients with the same protocol, requiring personalized management. The versatility of extracellular vesicles (EVs) and their contribution to sepsis progression bring along promises for one-to-one tailoring sepsis treatment and diagnosis. In this article, we critically review the endogenous role of EVs in sepsis progression and how current advancements have improved EVs-based therapies toward their translational future clinical application, with innovative strategies to enhance EVs effect. More complex approaches, including hybrid and fully synthetic nanocarriers that mimic EVs, are also discussed. Several pre-clinical and clinical studies are examined through the review to offer a general outlook of the current and future perspectives of EV-based sepsis diagnosis and treatment.

We have developed a new method to measure the viscosity of micrometric films by thermomechanical analysis with a hemispherical probe of millimetric diameter. The loading curve (displacement vs. time) recorded as the probe tip crosses the whole film at constant load until it touches the substrate is fitted to a theoretical curve shape that has been obtained after solving the problem of liquid flow under the probe tip. The method has been validated by measuring the viscosity of rosin films. It has been applied to analyze the thermal evolution of unstable liquid films that appear on Ba propionate, Ce(III) propionate and a low-fluorine precursor film of YBa2Cu3O6+x. During pyrolysis of the last two films, viscosity first diminishes due to heating and then it increases as solid oxide particles are formed inside the liquid.

Correction: Frontiers in Zoology 17, 13 (2020) https://doi.org/10.1186/s12983-020-00360-2 Following publication of the original article [1], the authors reported that the funding information has to be updated. The correct funding information should read: This study was supported by project CGL2015-71378-P MINECO/FEDER, UE, the Severo Ochoa Program (SVP-2014-068732) and Action COST ES1304 (ParrotNet). Logistical and technical support for fieldwork was provided by Doñana ICTS-RBD. The original article [1] has been updated.

The directed migration of cellular clusters enables morphogenesis, wound healing and collective cancer invasion. Gradients of substrate stiffness direct the migration of cellular clusters in a process called collective durotaxis, but the underlying mechanisms remain unclear. Here we unveil a connection between collective durotaxis and the wetting properties of cellular clusters. We show that clusters of cancer cells dewet soft substrates and wet stiff ones. At intermediate stiffness—at the crossover from low to high wettability—clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient and actomyosin activity. We demonstrate this behaviour on substrates coated with the cell–cell adhesion protein E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop an active wetting model that explains collective durotaxis in terms of a balance between in-plane active traction and tissue contractility and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a physical mechanism of collective durotaxis, through both cell–cell and cell–substrate adhesion ligands, based on the wetting properties of active droplets.

Iberian hare populations have suffered severe declines during recent decades in Spain. Between 1970 and 1990s, a rapid increase in irrigation crop surface in NW Spain (Castilla-y-León region) was followed by a common vole massive range expansion and complete colonization of lowland irrigated agricultural landscapes from mountainous habitats. The subsequent large cyclic fluctuations in abundance of colonizing common voles have contributed to a periodic amplification of Francisella tularensis, the etiological agent that causes human tularemia outbreaks in the region. Tularemia is a fatal disease to lagomorphs, so we hypothesize that vole outbreaks would lead to disease spill over to Iberian hares, increasing prevalence of tularemia and declines among hare populations. Here we report on the possible effects that vole abundance fluctuations and concomitant tularemia outbreaks had on Iberian hare populations in NW Spain. We analysed hare hunting bag data for the region, which has been recurrently affected by vole outbreaks between 1996 and 2019. We also compiled data on F. tularensis prevalence in Iberian hares reported by the regional government between 2007 and 2016. Our results suggest that common vole outbreaks may limit the recovery of hare populations by amplifying and spreading tularemia in the environment. The recurrent rodent-driven outbreaks of tularemia in the region may result in a "disease pit" to Iberian hares: at low host densities, the rate of population growth in hares is lower than the rate at which disease-induced mortality increases with increased rodent host density, therefore, keeping hare populations on a low-density equilibrium. We highlight future research needs to clarify tularemia transmission pathways between voles and hares and confirm a disease pit process.

Next-Generation Sequencing is needed for the accurate genetic risk stratification of acute myeloid leukemia according to European LeukemiaNet (ELN) guidelines. We validated and compared the 2022 ELN risk classification in a real-life cohort of 546 intensively and 379 non-intensively treated patients. Among fit patients, those aged ≥65 years old showed worse OS than younger regardless risk classification. Compared with the 2017 classification, 14.5% of fit patients changed the risk with the 2022 classification, increasing the high-risk group from 44.3% to 51.8%. 3.7% and 0.9% FLT3-ITD mutated patients were removed from the favorable and adverse 2017 categories respectively to 2022 intermediate risk group. We suggest that midostaurin therapy could be a predictor for 3 years OS (85.2% with vs. 54.8% without midostaurin, P = 0.04). Forty-seven (8.6%) patients from the 2017 intermediate group were assigned to the 2022 adverse-risk group as they harbored myelodysplasia (MDS)-related mutations. Patients with one MDS-related mutation did not reach median OS, while patients with ≥2 mutations had 13.6 months median OS (P = 0.002). Patients with TP53 ± complex karyotype or inv(3) had a dismal prognosis (7.1 months median OS). We validate the prognostic utility of the 2022 ELN classification in a real-life setting providing supportive evidences to improve risk stratification guidelines.

Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins—including gene expression, chromatin occupancy and three-dimensional conformation—we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.

Gut microbial composition plays an important role in numerous traits, including immune response. Integration of host genomic information with microbiome data is a natural step in the prediction of complex traits, although methods to optimize this are still largely unexplored. In this paper, we assess the impact of different modelling strategies on the predictive capacity for six porcine immunocompetence traits when both genotype and microbiota data are available.

Morphogenesis of the Central Nervous System (CNS) is a complex process that obeys precise architectural rules. Yet, the mechanisms dictating these rules remain unknown. Analyzing morphogenesis of the Drosophila embryo Ventral Nerve Cord (VNC), we observe that a tight control of JNK signaling is essential for attaining the final VNC architecture. JNK signaling in a specific subset of pioneer neurons autonomously regulates the expression of Fasciclin 2 (Fas 2) and Neurexin IV (Nrx IV) adhesion molecules, probably via the transcription factor zfh1. Interfering at any step in this cascade affects fasciculation along pioneer axons, leading to secondary cumulative scaffolding defects during the structural organization of the axonal network. The global disorder of architectural landmarks ultimately influences nervous system condensation. In summary, our data point to JNK signaling in a subset of pioneer neurons as a key element underpinning VNC architecture, revealing critical milestones on the mechanism of control of its structural organization.

In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair.

Post-harvest fruit and vegetable rot produced by Botrytis cinerea (Helotiales: Sclerotiniaceae) causes significant reductions in food availability and drastically increases economic losses. The use of microbial-based tools for pathogen management holds promise. In particular, volatile organic compounds (VOCs) emitted by microbes (e.g., bacterial compounds) are becoming increasingly more frequent as an alternative to chemical and physical treatments. In this study, we performed three laboratory experiments to investigate the effects of VOCs emitted by two gram-negative entomopathogenic bacteria, Xenorhabdus nematophila, and Photorhabdus laumondii subsp. laumondii, on the infection and growth of the pathogenic mold B. cinerea on post-harvest red grapes and tomatoes. In addition, we evaluated the preventive effects of these bacterial VOCs against pathogens in post-harvest wounded and intact grapes. Overall, VOCs emitted by X. nematophila and P. laumondii limited the lesion area of B. cinerea to 0.5% and 2.2%, respectively, on the grapes. Similarly, VOCs emitted by X. nematophila and P. laumondii limited the lesion area of B. cinerea to 0.5% and 0.02%, respectively, in tomatoes. In addition, the emission of VOCs by both bacteria showed strong preventive fungal effects. In particular, VOCs emitted by P. laumondii reduced to 13% B. cinerea incidence in damaged grapes exposed to VOCs. Moreover, intact grapes exposed to VOCs emitted by X. nematophila and P. laumondii decreased B. cinerea incidence by 33%. This study provides insightful information about a potential novel bacteria-based tool that can be used as an alternative in the integrated control of post-harvest diseases.

[EN] In Europe, many bird populations have undergone strong declines over the last decades. The European Turtle Dove is an iconic declining bird species that can be legally hunted in ten EU countries, with hundreds of thousands of birds being harvested annually in western Europe alone. The European Union urgently required from these member states to tackle illegal and legal unsustainable hunting to support migratory bird conservation (BirdLife International in European red list of birds. Office for Official Publications of the European Communities, Luxembourg. http://www.iucnredlist.org/details/22690419/1, 2021), and to consider that a careful regulation of harvest for declining hunted species should be the norm. In this study, we investigated turtle dove population dynamics in the western European flyway. The objective was to assess the current population growth rate, the relative importance of survival, and fecundity in determining prospective turtle dove population change, and to quantify the current level of harvest at the western flyway scale. We developed a population model including recent estimates of vital rates obtained from the core of the breeding distribution in the western flyway. The outputs of the model reproduced the declining trend of the European Turtle Dove and identified a predominant role of survival on prospective population dynamics, implying a potential positive effect of hunting regulation on population growth. Our results support the idea that actions increasing survival, among which hunting regulation, may be an important leverage for population management in this species. This study represents a major step towards a thoughtful adaptive management approach of the turtle dove population, and could be used as a template for other declining hunted bird species., [DE] In Europa haben viele Vogelpopulationen in den letzten Jahrzehnten einen starken Rückgang erfahren. Die Turteltaube (Streptopelia turtur) ist eine besonders stark vom Aussterben bedrohte Vogelart, die in 10 EU-Ländern legal gejagt werden kann, mit jährlich Hunderttausenden von nur allein in Westeuropa erlegten Tieren. Die Europäische Union forderte die betreffenden zehn Mitgliedstaaten dringend auf, die illegale und auch legale, aber nicht nachhaltige, Jagd zum Schutz der Zugvögel zu unterbinden (BirdLife International 2021) und darüber nachzudenken, dass eine schonende Regulierung der Jagd für solche vom Aussterben bedrohte Arten zur Norm erhoben weden sollte. In dieser Studie untersuchten wir die Populationsdynamik von Turteltauben auf ihrer westeuropäischen Zugroute. Ziel war es, die derzeitige Wachstumsrate der Population, die relative Bedeutung von Überleben und Fruchtbarkeit bei der Bestimmung der voraussichtlichen Populationsveränderung der Turteltaube zu bewerten und das derzeitige Ausmaß ihrer Bejagung auf der westlichen Zugroute zu quantifizieren. Wir entwickelten ein Populationsmodell mit aktuellen Schätzungen der Vitalitätsraten aufgrund von Daten aus den Haupt-Brutgebieten auf der westlichen Zugroute. Die Ergebnisse des Modells bestätigten den rückläufigen Trend bei der Europäischen Turteltaube und ergaben, dass die Überlebensrate bei der zukünftigen Populationsdynamik eine vorherrschende Rolle spielt, was eine potenziell positive Auswirkung der Regulierung der Bejagung auf das Populationswachstum nahelegt. Unsere Ergebnisse unterstützen die Annahme, dass Maßnahmen zur Erhöhung der Überlebensrate, darunter die Regulierung der Jagd, ein wichtiger Ausgangspunkt für das Bestandsmanagement bei dieser Art sein können. Die Studie stellt einen wichtigen Schritt in Richtung eines wohlüberlegten, angepassten Managementansatzes für die Turteltaubenpopulation dar und könnte als Modell für andere rückläufige, bejagte Vogelarten dienen.

Triticum turgidum ssp. dicoccoides (wild emmer wheat) was one of the first plants that gave rise to domestic wheat forms in southwest Asia. The details of the domestication of emmer and its early dispersal routes out of southwest Asia remain elusive, especially with regard to its dispersal to the east. In this study, we combine whole genome data from a selection of specimens of modern wild T. turgidum ssp. dicoccoides and domestic T. turgidum ssp. dicoccum (emmer wheats) with a previously published 3,000 year old sample, to explore the phylogenetic relationships between wild and domestic populations of emmer, and especially the early dispersal routes south and eastwards to Africa and Asia, respectively. Our data confirm a marked differentiation between landraces from Europe, the Caucasus and Iran, and those from Africa, the Arabian Peninsula and India, the first group being more closely related to wild emmer from the northern and eastern Fertile Crescent. Gene flow is detected between wild emmer from the western Fertile Crescent and the second group of domestic emmer. These results support a dispersal route from southwest Asia to Africa, the Arabian Peninsula and India. We also observe a lower genetic variability in the wild emmer from the northern and eastern compared with that of the western Fertile Crescent. It is possible that the ancestors of domestic emmer that spread into Egypt still remain to be surveyed and analysed. Investigating the genetic content of ancient samples from Europe, the Caucasus or Iran would be very valuable to determine whether the two distinct types of germplasm arose during history or were already present during the early phases of dispersal.

Gaining more insights on how R&D&i subsidies are allocated is highly relevant for companies and policymakers. This article provides new evidence of the identification of some key drivers for companies participating in R&D&i project selection processes. It extends the existing literature by providing insight based on sophisticated, accurate methodology. A metaheuristic optimization algorithm is employed to select the most useful variables. Their importance is then ranked using a machine learning process, namely a random forest. A sample of 1252 cases of R&D&i subsidies is used for more than 800 companies based in Spain between 2014 and 2018. The study contributes by providing useful knowledge into how the value of received subsidies are associated with some firm characteristics. The findings allow the implementation of transparent public innovation policies and the reduction of the gap between the aspects that are considered important and those that actually determine the destination of these subsidies.

Environmental pollution caused by polycyclic aromatic hydrocarbons (PAHs) involves a high-risk and have received considerable attention due to their carcinogenic, teratogenic, and mutagenic properties. Phenanthrene (PHE) is a low molecular weight PAH, which has three benzene rings. It is one of the most common PAH found in contaminated environments mainly due to its low volatilization ability and hydrophobic character. A PHE degrading bacterium was isolated from an industrial contaminated soil using enrichment culture techniques. Based on macroscopic, microscopic examination and phylogenetic analysis, this bacterium was classified as Stenotrophomonas indicatrix and named strain CPHE1. Several authors have reported about bacteria stains, which can degrade PHE, but this is the first time where the ability of S. indicatrix to biodegrade and mineralize PHE has been demonstrated.

We checked the effect of biochar addition to a fertile temperate soil on plant growth and the quantity and quality of seeds of four varieties of wheat (Triticum spp., two “ancient” varieties, Verna and Senatore Cappelli, and two “modern” varieties, Bologna and Claudio) and a high oleic hybrid of sunflower (Helianthus annuus L.). Relatively novel is the qualitative investigation of the marketable product, as few are the works on this topic. We tested three different doses of biochar—1, 4, and 20 t ha−1—versus an untreated soil (“control”) in a 2-year open field trial in Central Italy, where wheat was grown the first year and sunflower the second year. Biochar addition did not change the soil characteristics save for the carbon content, which increased significantly with the highest dose of biochar. Also, we did not find any significant biochar-induced effect on plant growth and yields of both wheat and sunflower. Regarding the qualitative aspects, adding biochar to the soil implied an increase in total polyphenols in the middlings and bran of wheat and, with the highest dose of biochar, also in total proteins and in flavonoids and caffeic acid derivatives. Instead, no difference in carotenoids concentration and antiradical activity was observed in middlings or bran. As for the sunflower, no significant difference in seeds’ composition was detected at any of the biochar doses. The addition of biochar to a fertile, well-drained soil as the one we investigated is not detrimental to the quantity and quality of wheat and sunflower seeds. Rather, the concentration of some polyphenols in wheat appears to be positively affected by biochar addition.

Detectability of morphs in different light environments is one of the mechanisms favoring the persistence of color polymorphism via disruptive selection. This mechanism predicts that different morphs should be more active and successful when light conditions make them more cryptic. In nocturnal birds, no study has analyzed yet whether morphs show a different degree of nocturnality, showing different circadian activity rhythms in relation to night and day light. We analyze activity patterns and hunting efficiency of color morphs in relation to day/night light in the nocturnal polymorphic scops owl (Otus scops). Forty-four percent of owl activity took place in the first hours after sunrise and before sunset. Also, we found that nocturnal activity decreased from grey to brown females and that grey males fed their chicks more than brown ones at night. Visual modeling revealed that grey individuals would be more conspicuous to their prey than brownish ones during the day. These findings suggest that part of the activity of nocturnal scops owls may occur during the day and that grey individuals would be better adapted to forage during night-light than brownish ones. However, brown morphs seemed not to be better adapted to forage at day, suggesting that other mechanisms than visual detection by predators or prey contribute to the persistence of color polymorphism in the species.

ATP-citrate lyase is a central integrator of cellular metabolism in the interface of protein, carbohydrate, and lipid metabolism. The physiological consequences as well as the molecular mechanisms orchestrating the response to long-term pharmacologically induced Acly inhibition are unknown. We report here that the Acly inhibitor SB-204990 improves metabolic health and physical strength in wild-type mice when fed with a high-fat diet, while in mice fed with healthy diet results in metabolic imbalance and moderated insulin resistance. By applying a multiomic approach using untargeted metabolomics, transcriptomics, and proteomics, we determined that, in vivo, SB-204990 plays a role in the regulation of molecular mechanisms associated with aging, such as energy metabolism, mitochondrial function, mTOR signaling, and folate cycle, while global alterations on histone acetylation are absent. Our findings indicate a mechanism for regulating molecular pathways of aging that prevents the development of metabolic abnormalities associated with unhealthy dieting. This strategy might be explored for devising therapeutic approaches to prevent metabolic diseases.

The dynamical behavior of complex quantum systems can be harnessed for information processing. With this aim, quantum reservoir computing (QRC) with Ising spin networks was recently introduced as a quantum version of classical reservoir computing. In turn, reservoir computing is a neuro-inspired machine learning technique that consists in exploiting dynamical systems to solve nonlinear and temporal tasks. We characterize the performance of the spin-based QRC model with the Information Processing Capacity (IPC), which allows to quantify the computational capabilities of a dynamical system beyond specific tasks. The influence on the IPC of the input injection frequency, time multiplexing, and different measured observables encompassing local spin measurements as well as correlations is addressed. We find conditions for an optimum input driving and provide different alternatives for the choice of the output variables used for the readout. This work establishes a clear picture of the computational capabilities of a quantum network of spins for reservoir computing. Our results pave the way to future research on QRC both from the theoretical and experimental points of view.

The COVID-19 pandemic spread around the world is due to the enormous capacity of the SARS-CoV-2 coronavirus to be transmitted between humans, causing a threat to global public health. It has been shown that the entry of this virus into cells is highly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Currently, we have no precise knowledge of how this receptor expresses in the brain of human fetus and, as a consequence, we do not know how susceptible the neural cells in the developing brain are to being infected through the vertical transmission of this virus, from mother to fetus. In this work, we describe the expression of ACE2 in the human brain at 20 weeks of gestation. This stage corresponds to the period of neuronal generation, migration, and differentiation in the cerebral cortex. We describe the specific expression of ACE2 in neuronal precursors and migratory neuroblasts of the dentate gyrus in the hippocampus. This finding implies that SARS-CoV-2 infection during the fetal period may affect neuronal progenitor cells and alter the normal development of the brain region where memory engrams are generated. Thus, although vertical transmission of SARS-CoV-2 infection was reported in few cases, the massive infection rate of young people in terms of the new variants leads to the possibility of increasing the ratio of congenital infections and originating cognitive alterations, as well as neuronal circuit anomalies that may represent vulnerability to mental problems throughout life.

Normal aging and many age-related disorders such as Alzheimer's disease cause deficits in olfaction; however, it is currently unknown how natural and pathological aging impacts the detection of social odors which might contribute to the impoverishment of social behavior at old age further worsening overall health. Analysis of the vomeronasal organ, the main gateway to pheromone-encoded information, indicated that natural and pathological aging distinctively affects the neurogenic ability of the vomeronasal sensory epithelium. Whereas cell proliferation remained majorly preserved in 1-year-old APP/PS1 mice, naturally aged animals exhibited significant deficiencies in the number of mature, proliferative, and progenitor cells. These alterations may support age-related deficits in the recognition of social cues and the display of social behavior. Our findings indicate that aging disrupts the processing of social olfactory cues decreasing social odor exploration, discrimination, and habituation in both wild-type senescent (2-year-old) mice and in 1-year-old double mutant model of Alzheimer's disease (APP/PS1). Furthermore, social novelty was diminished in 1-year-old APP/PS1 mice, indicating that alterations in the processing of social cues are accelerated during pathological aging. This study reveals fundamental differences in the cellular processes by which natural and pathological aging disrupts the exploration of social information and social behavior.

Citizen science invites the public to participate in both scientific thinking and data collection. Citizen science adds new collaborators whose contributions help to gather or analyse data on a large scale particularly relevant for emerging questions about the distribution and abundance of organisms across space and time. Syngnathids are cryptic fishes that inhabits temperate and tropical sheltered, coastal marine waters. Pipefishes and seahorses are threatened by habitat loss and degradation. Unfortunately, data on biological and ecological aspects and population trends are rarely available in most species. More than half of the thirteen-syngnathid species inhabiting Spanish coasts are considered Data Deficient for population evaluation. Citizen science is an opportunity to improve data availability for the study of syngnathid population tendencies and monitoring. This contribution describes and discusses the approach followed by Sea Watchers citizen science platform. We analysed and discussed the data provided by the observers, and the distribution data of species based on citizen science surveillance. Citizen science achieved the expansion of spatial and temporal dataset of syngnathid distribution. However, the obtained information is affected by observers’ behaviour and suggest that the observers performed focussed surveys to find individuals of these slow motion iconic fishes, introducing biases in the data.

Understanding the global and dynamic nature of plant developmental processes requires not only the study of the transcriptome, but also of the proteome, including its largely uncharacterized peptidome fraction. Recent advances in proteomics and high-throughput analyses of translating RNAs (ribosome profiling) have begun to address this issue, evidencing the existence of novel, uncharacterized, and possibly functional peptides. To validate the accumulation in tissues of sORF-encoded polypeptides (SEPs), the basic setup of proteomic analyses (i.e., LC-MS/MS) can be followed. However, the detection of peptides that are small (up to ~100 aa, 6–7 kDa) and novel (i.e., not annotated in reference databases) presents specific challenges that need to be addressed both experimentally and with computational biology resources. Several methods have been developed in recent years to isolate and identify peptides from plant tissues. In this chapter, we outline two different peptide extraction protocols and the subsequent peptide identification by mass spectrometry using the database search or the de novo identification methods.

Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that ß-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VEcadherin upon FAK disabling resulted in VE-Cadherin/ß-catenin complex dissociation, increased ß-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses ß-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits stabilization of ß-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the cooperation of ß-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.

Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders.

Long-term regional climate simulations are computationally very costly. One way to improve their computational efficiency is to split them into overlapping time slices, which can then be run in parallel. Although this procedure reduces the cost, sufficient spin-up must be left at the start of each slice. In any case, discontinuities will occur due to internal variability where two different slices join. In this study, we explore the relative role of spin-up time and internal variability in the discontinuities of overlapping time slice simulations and their effect on the simulated climate. This analysis has implications also for non-overlapping time slices, commonly used in very high resolution climate modelling, where long transient simulations cannot be afforded. We show that discontinuities are negligible for surface and upper-air variables, but they are noticeable in variables with long response times, such as soil moisture or snow depth. For these variables, differences between the slices are mainly attributed to internal variability, but also to insufficient spin-up time, depending on the region. In general, the results show that the overlapping time slice approach is valid to accomplish long term regional climate simulations.

Microorganisms are ubiquitously distributed in nature and usually appear as biofilms attached to a variety of surfaces. Here, we report the development of a thick biofilm in the drain pipe of several standard laboratory ice machines, and we describe and characterise, through culture-dependent and -independent techniques, the composition of this oligotrophic microbial community. By using culturomics, 25 different microbial strains were isolated and taxonomically identified. The 16S rRNA high-throughput sequencing analysis revealed that Bacteroidota and Proteobacteria were the most abundant bacterial phyla in the sample, followed by Acidobacteriota and Planctomycetota, while ITS high-throughput sequencing uncovered the fungal community was clearly dominated by the presence of a yet-unidentified genus from the Didymellaceae family. Alpha and beta diversity comparisons of the ice machine microbial community against that of other similar cold oligotrophic and/or artificial environments revealed a low similarity between samples, highlighting the ice machine could be considered a cold and oligotrophic niche with a unique selective pressure for colonisation of particular microorganisms. The recovery and analysis of high-quality metagenome-assembled genomes (MAGs) yielded a strikingly high rate of new species. The functional profiling of the metagenome sequences uncovered the presence of proteins involved in extracellular polymeric substance (EPS) and fimbriae biosynthesis and also allowed us to detect the key proteins involved in the cold adaptation mechanisms and oligotrophic metabolic pathways. The metabolic functions in the recovered MAGs confirmed that all MAGs have the genes involved in psychrophilic protein biosynthesis. In addition, the highest number of genes for EPS biosynthesis was presented in MAGs associated with the genus Sphingomonas, which was also recovered by culture-based method. Further, the MAGs with the highest potential gene number for oligotrophic pro

[Background and objective] Patients with young-onset Parkinson’s disease (YOPD) have a slower progression. Our aim was to analyze the change in cognitive function in YOPD compared to patients with a later onset and controls., [Patients and methods] Patients with Parkinson’s disease (PD) and controls from the COPPADIS cohort were included. Cognitive function was assessed with the Parkinson’s Disease Cognitive Rating Scale (PD-CRS) at baseline (V0), 2-year ± 1 month (V2y), and 4-year ± 3 months follow-up (V4y). Regarding age from symptoms onset, patients were classified as YOPD (< 50 years) or non-YOPD (≥ 50). A score in the PD-CRS < 81 was defined as cognitive impairment (CI): ≤ 64 dementia; 65–80 mild cognitive impairment (MCI)., [Results] One-hundred and twenty-four YOPD (50.7 ± 7.9 years; 66.1% males), 234 non-YOPD (67.8 ± 7.8 years; 59.3% males) patients, and 205 controls (61 ± 8.3 years; 49.5% males) were included. The score on the PD-CRS and its subscore domains was higher at all visits in YOPD compared to non-YOPD patients and to controls (p < 0.0001 in all analysis), but no differences were detected between YOPD patients and controls. Only non-YOPD patients had significant impairment in their cognitive function from V0 to V4y (p < 0.0001). At V4y, the frequency of dementia and MCI was 5% and 10% in YOPD compared to 25.2% and 22.3% in non-YOPD patients (p < 0.0001). A lower score on the Parkinson’s Disease Sleep Scale at baseline was a predictor of CI at V4y in YOPD patients (Adjusted R2 = 0.61; OR = 0.965; p = 0.029)., [Conclusion] Cognitive dysfunction progressed more slowly in YOPD than in non-YOPD patients.

Nesting events of loggerhead sea turtles (Caretta caretta) are on the rise in the Western Mediterranean Sea, far from their usual nesting areas in the Mediterranean and Atlantic basins. The study of dispersal behavior toward potential developmental areas of loggerhead post-hatchlings from this new nesting area is crucial to comprehend this colonization process and determining grounded conservation strategies. To fill this gap, we investigated, for the first time in the Mediterranean Sea, the dispersal strategies and habitat use based on data from 19 head-started loggerhead post-hatchlings released from the Spanish Mediterranean coast and satellite-tracked between 2016 and 2018. Turtles dispersed over large areas and showed active swimming phases, as they frequently dispersed against sea currents. Dispersal routes varied for each individual, although they consistently dispersed south-eastwards, especially during the coldest periods. Several post-hatchlings traveled through the Sicilian Channel to reach deep and warmer areas in the eastern Mediterranean basin. The most year-round suitable areas corresponded to the Ionian and Levantine Seas, which correspond with those found in their traditional nesting areas. Therefore, conservation measures focused on this stage should be taken in the path toward and these developmental areas.

The ongoing mobilization of active non-long terminal repeat (LTR) retrotransposons continues to impact the genomes of most mammals, including humans and rodents. Non-LTR retrotransposons mobilize using an intermediary RNA and a copy-and-paste mechanism termed retrotransposition. Non-LTR retrotransposons are subdivided into long and short interspersed elements (LINEs and SINEs, respectively), depending on their size and autonomy; while active class 1 LINEs (LINE-1s or L1s) encode the enzymatic machinery required to mobilize in cis, active SINEs use the enzymatic machinery of active LINE-1s to mobilize in trans. The mobilization mechanism used by LINE-1s/SINEs was exploited to develop ingenious plasmid-based retrotransposition assays in cultured cells, which typically exploit a reporter gene that can only be activated after a round of retrotransposition. Retrotransposition assays, in cis or in trans, are instrumental tools to study the biology of mammalian LINE-1s and SINEs. In fact, these and other biochemical/genetic assays were used to uncover that endogenous mammalian LINE-1s/SINEs naturally retrotranspose during early embryonic development. However, embryonic stem cells (ESCs) are typically used as a cellular model in these and other studies interrogating LINE-1/SINE expression/regulation during early embryogenesis. Thus, human and mouse ESCs represent an excellent model to understand how active retrotransposons are regulated and how their activity impacts the germline. Here, we describe robust and quantitative protocols to study human/mouse LINE-1 (in cis) and SINE (in trans) retrotransposition using (human and mice) ESCs. These protocols are designed to study the mobilization of active non-LTR retrotransposons in a cellular physiologically relevant context.

We provide the first whole genome Copy Number Variant (CNV) study addressing Roma, along with reference populations from South Asia, the Middle East and Europe. Using CNV calling software for short-read sequence data, we identified 3171 deletions and 489 duplications. Taking into account the known population history of the Roma, as inferred from whole genome nucleotide variation, we could discern how this history has shaped CNV variation. As expected, patterns of deletion variation, but not duplication, in the Roma followed those obtained from single nucleotide polymorphisms (SNPs). Reduced effective population size resulting in slightly relaxed natural selection may explain our observation of an increase in intronic (but not exonic) deletions within Loss of Function (LoF)-intolerant genes. Over-representation analysis for LoF-intolerant gene sets hosting intronic deletions highlights a substantial accumulation of shared biological processes in Roma, intriguingly related to signaling, nervous system and development features, which may be related to the known profile of private disease in the population. Finally, we show the link between deletions and known trait-related SNPs reported in the genome-wide association study (GWAS) catalog, which exhibited even frequency distributions among the studied populations. This suggests that, in general human populations, the strong association between deletions and SNPs associated to biomedical conditions and traits could be widespread across continental populations, reflecting a common background of potentially disease/trait-related CNVs.