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Abstract Background Battling malaria’s morbidity and mortality rates demands innovative methods related to malaria diagnosis. Thick blood smears (TBS) are the gold standard for diagnosing malaria, but their coloration quality is dependent on supplies and adherence to standard protocols. Machine learning has been proposed to automate diagnosis, but the impact of smear coloration on parasite detection has not yet been fully explored. Methods To develop Coloration Analysis in Malaria (CAM), an image database containing 600 images was created. The database was randomly divided into training (70%), validation (15%), and test (15%) sets. Nineteen feature vectors were studied based on variances, correlation coefficients, and histograms (specific variables from histograms, full histograms, and principal components from the histograms). The Machine Learning Matlab Toolbox was used to select the best candidate feature vectors and machine learning classifiers. The candidate classifiers were then tuned for validation and tested to ultimately select the best one. Results This work introduces CAM, a machine learning system designed for automatic TBS image quality analysis. The results demonstrated that the cubic SVM classifier outperformed others in classifying coloration quality in TBS, achieving a true negative rate of 95% and a true positive rate of 97%. Conclusions An image-based approach was developed to automatically evaluate the coloration quality of TBS. This finding highlights the potential of image-based analysis to assess TBS coloration quality. CAM is intended to function as a supportive tool for analyzing the coloration quality of thick blood smears.

Abstract Background Therapeutic ceiling of care is the maximum level of care deemed appropiate to offer to a patient based on their clinical profile and therefore their potential to derive benefit, within the context of the availability of resources. To our knowledge, there are no models to predict ceiling of care decisions in COVID-19 patients or other acute illnesses. We aimed to develop and validate a clinical prediction model to predict ceiling of care decisions using information readily available at the point of hospital admission. Methods We studied a cohort of adult COVID-19 patients who were hospitalized in 5 centres of Catalonia between 2020 and 2021. All patients had microbiologically proven SARS-CoV-2 infection at the time of hospitalization. Their therapeutic ceiling of care was assessed at hospital admission. Comorbidities collected at hospital admission, age and sex were considered as potential factors for predicting ceiling of care. A logistic regression model was used to predict the ceiling of care. The final model was validated internally and externally using a cohort obtained from the Leeds Teaching Hospitals NHS Trust. The TRIPOD Checklist for Prediction Model Development and Validation from the EQUATOR Network has been followed to report the model. Results A total of 5813 patients were included in the development cohort, of whom 31.5% were assigned a ceiling of care at the point of hospital admission. A model including age, COVID-19 wave, chronic kidney disease, dementia, dyslipidaemia, heart failure, metastasis, peripheral vascular disease, chronic obstructive pulmonary disease, and stroke or transient ischaemic attack had excellent discrimination and calibration. Subgroup analysis by sex, age group, and relevant comorbidities showed excellent figures for calibration and discrimination. External validation on the Leeds Teaching Hospitals cohort also showed good performance. Conclusions Ceiling of care can be predicted with great accuracy from a patient’s clinical information available at the point of hospital admission. Cohorts without information on ceiling of care could use our model to estimate the probability of ceiling of care. In future pandemics, during emergency situations or when dealing with frail patients, where time-sensitive decisions about the use of life-prolonging treatments are required, this model, combined with clinical expertise, could be valuable. However, future work is needed to evaluate the use of this prediction tool outside COVID-19.

Abstract Cyanobacterial phycocyanin and phycoerythrin are gaining commercial interest due to their nutrition and healthcare values. This research analyzed the biomass accumulation and pigment production of two strains of Leptolyngbya under different combinations of light colors and intensities. The results showed that while Leptolyngbya sp.4 B1 (B1) produced all phycobiliproteins, Leptolyngbya sp.5 F2 (F2) only had phycocyanin and allophycocyanin. Both the color of the light and its light intensity affect the biomass accumulation and phycoerythrin concentration in strain B1. Although white light at medium intensity (50 μmol m-2 s-1) causes greater biomass accumulation (1.66 ± 0.13 gDW L-1), low-intensity (25 μmol m-2 s-1) green light induces lower biomass accumulation with twice the pigment content (87.70 ± 2.46 mg gDW -1), culminating in 71% greater productivity. In contrast, for the F2 strain, light intensity positively influenced biomass and pigment accumulation, being observed 2.25 ± 0.10 gDW L-1 under white light at 100 μmol m-2 s-1 and higher phycocyanin concentration (138.38 ± 3.46 mg gDW -1) under red light at 100 μmol m-2 s-1. These findings provide insights into optimizing the growth conditions by altering the intensity and wavelength of light for future production of phycocyanin and phycoerythrin from local cyanobacteria.

The field of bioinspired underwater robots aims to replicate the capabilities of marine animals in artificial systems. Stingrays have emerged as highly promising species to be mimicked because of their flat body morphology and size. Furthermore, they are considered high-performance species due to their maneuverability, propulsion mode, and sliding efficiency. Designing and developing mechanisms to imitate their pectoral fins is a challenge for underwater robotic researchers mainly because the locomotion characteristics depend on the coordinated movement of the fins. In the state of the art, several mechanisms were proposed with 2 active rotation degrees of freedom (DoFs) to replicate fin movement. In this paper, we propose adding an additional active DoF in order to improve the realism in the robotic manta ray movement. Therefore, in this article, we present the mechanical design, modeling, and kinematics analysis of a 3-active-and-rotational-DoF pectoral fin inspired by the Mobula Alfredi or reef manta ray. Additionally, by using the kinematics model, we were able to simulate and compare the behaviour of both mechanisms, that is, those with 2 and 3 DoFs. Our simulation results reveal an improvement in the locomotion, and we hypothesized that with the third DoF, some specific missions, such as hovering or fast emergence to the surface, will have a better performance.

Phellinotus (Polyporales) is a common genus of wood-decay fungi in tropical and subtropical areas, endemic to the Seasonally Dry Tropical Forest (SDTF) biome. However, Phellinotus diversity remains unexplored, despite being a major threat to living trees. Therefore, this study is aimed at confirming and characterizing through morphological and molecular data the first isolates of Phellinotus teixeirae in Pithecellobium dulce (Fabaceae) trees (locally referred to as ‘Chiminango’) from the endangered Colombian SDTF biome. Fifteen fungal specimens were recovered from living P. dulce trees, in the urban area and at the Universidad del Valle campus, and classified as P. teixeirae based on taxonomical descriptors. Phylogenetic relationships were inferred from a four-loci dataset (ribosomal and gene-coding regions), including 82 taxa covering 3991 nucleotide positions. The analysis recovered seven highly supported (>90% bootstrapping) monophyletic taxa of the ‘Phellinotus Clade’, and confirmed the new distribution range of P. teixeirae (100% bootstrap support), which extends approx. 1000 km north in the Neotropics. Hierarchical stratified Analysis of MOlecular VAriance (AMOVA) provided a clear genetic distinction between species (70% of variation, p-value = 0.001) and low differentiation among country of origin within species (11%, p-value = 0.044). Discriminant Analysis for Principal Components (DAPC) indicated complex clustering including closely related species, probably a signal of recent radiation and weak species boundaries. Median-joining haplotype network analysis identified unique haplotypes, which may correlate with new host colonization and population expansion (Tajima’s D ≤ −0.5). In conclusion, this study provides the first assessment of the genetic diversity of P. teixeirae in a novel geography (SDTP) and host tree (P. dulce). However, increasing the number of isolates remains critical to understand further the genus’ distribution patterns and drivers of genetic diversity.

This paper offers the basic guidelines of a formalized version of the Lexical Constructional Model (LCM; Ruiz de Mendoza & Mairal Usón, 2008, 2011; Ruiz de Mendoza & Galera, 2014), the Formalized Lexical-Constructional Grammar (FL_CxG), which will pave the way for future computational developments, such as parsers or lexical databases. The FL_CxG deploys (i) the typologically oriented syntactic apparatus of Role and Reference Grammar (Van Valin, 2005; Van Valin & LaPolla, 1997), (ii) the catalogue of constructional units arranged in a 4-layer typology, as proposed by the LCM, and (iii) some insights for semantic representations from the Generative Lexicon Theory (Pustejovsky, 1995; Pustejovsky & Batiukova, 2019), and Minimal English (Goddard, 2018). All the components of the FL_CxG (lexical units and construct(ion)s) are formally encoded as Typed Feature Structures in the format of Attribute Value Matrixes. These units are to be understood as constraints operating in the unification processes which underlie the generation/decoding of a given fragment of language.

The high mountain forests on Earth are characterized by sharp environmental heterogeneity, high species endemism, and unique phenotypic adaptations. Yet, global warming is jeopardizing this ecosystem as no other as some forests may have nowhere to go beyond the mountain’s summits. One of the most human-endangered high-elevation ecosystems is the Polylepis forest. Despite its vulnerability, forecasting climate reactions in this distinctive high mountain forest type remains a formidable challenge. Therefore, in this study, we modeled climate change responses of high-elevation allopatric Polylepis sericea and P. quadrijuga (Rosaceae) in the northern Andes. The analysis took into account VIF-prioritized bioclimatic variables for near-to-present and future (2081–2100 MPI-ESM1-2-HR) conditions. Model selection was carried out following the AUC scores of 12 MaxEnt and six machine learning algorithms. Predictive power reached 0.97 for MaxEnt’s model fc.H_rm.1 (H-1). Results indicate a moderate vulnerability of P. sericea, with a 29% loss of area in the trailing edge, due to climate change for the period 2081–2100. On the other hand, P. quadrijuga is likely to experience even larger distribution losses, up to 99%, for the same period. The findings of this study suggest that P. quadrijuga, as compared to P. sericea, exhibits a restricted ability to maintain the corresponding habitat requirements in the face of climatic change. Higher niche specialization of P. quadrijuga in the environmentally heterogeneous Eastern Cordillera contrasts with the more generalist nature of P. sericea in the topographically less complex Central Cordillera. In addition to climate change, this trend may be exacerbated by the detrimental effects of agriculture, mining, and an expanding rural population, which represent significant human-driven pressures yet to be modeled in the northern Andean highlands. Yet, based on previous studies, the historical population dynamics during the past glacial cycles suggests that range shifts could play a more significant role at deeper time scales than previously forecasted in the species’ reaction to climate change. Additionally, Polylepis forests may be able to endure at the current locations via local adaptation and plasticity, major drivers of the phenotypic variation in long-lived trees, counteracting the vulnerability scenario under a niche conservatism hypothesis. Ultimately, the modeling procedure employed in this study provides insights into the potential effects of climate change on Polylepis forests 70 years from now. Oncoming studies may consider alternative responses inherent to the gene pool of the species and the interaction with edaphic and biotic agents. We advocate for the application of comparable estimations in other high-elevation tree communities found at the tree line.

Plant breeding [...]

Cowpea is one of the most popular dry-land legumes cultivated for food and forage in arid and semi-arid areas. Genetic diversity for global germplasm can be organized into core collections providing optimum resources to serve breeding requirements. Here, we present diversity analysis and genome-wide association study (GWAS) results for part of the cowpea core collection of the United States Department of Agriculture (USDA) along with breeding line controls. Included in the analysis were a total of 373 accessions analyzed with 6880 Single Nucleotide Polymorphism (SNP) markers from Genotyping by Sequencing (GBS). Population structure differentiated accessions into two groups irrespective of geographical origin and formed three clusters based on taxa upon phylogenetic analysis. A total of 56 SNPs were significantly associated to nine traits including pod length (25 Quantitative Trait Nucleotides, QTNs), seed anti-oxidant content (7 QTNs), dry pod color (7 QTNs), plant maturity (5 QTNs), flower color (5 QTNs), seed weight (4 QTNs), tolerance to low phosphate (1 QTN), growth habit (1 QTN), and response to rock phosphate (1 QTN) using Bayesian-information, Linkage-disequilibrium Iteratively Nested Keyway (BLINK), and Fixed and random model Circulating Probability Unification (FarmCPU) association models. Key genes related to all significant SNPs were identified based on annotations of the cowpea reference genome, including a flavonoid gene controlling flower color (Vigun08g040200.1), a root nodulation regulator for tolerance to low phosphate (Vigun11g168000.1), and numerous genes involved in signaling, biosynthesis, metabolite transport, and abiotic stress. Our results highlight the importance of maintaining public phenotyping databases at USDA and strengthening collaborations for data collection in cowpea to maximize research impacts.

This paper presents the results of a quantitative study of adjuncts in the Airbus corpus carried out within the theoretical framework of Role and Reference Grammar (RRG). We describe the positional behaviour of these peripheral constituents in the Layered Structure of the Clause and postulate scales of positional and peripheral preferences, based on frequency distribution, in the Airbus controlled natural language (CNL). The results obtained were compared with a previous study on adjunct preferences and positions in Natural English to check for changes in these scales due to the nature of the texts written in this CNL. We also aim to contribute to the development of the RRG analysis of adverbials by offering a detailed semantic typology and a description of the syntax of these peripheral constituents grounded in empirical and quantitatively based data that will serve as a basis for the parsing of adverbials in the computational processing of CNLs.

Abstract Background We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. Methods HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. Results Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon’s design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5–32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. Conclusion Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. Trial registration ClinicalTrials.gov and EudraCT (NCT03025880 and 2016–001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; 1H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., Escherichia coli and Akkermansia muciniphila) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.

Disruptions of the light/dark cycle and unhealthy diets can promote misalignment of biological rhythms and metabolic alterations, ultimately leading to an oxidative stress condition. Grape seed proanthocyanidin extract (GSPE), which possesses antioxidant properties, has demonstrated its beneficial effects in metabolic-associated diseases and its potential role in modulating circadian disruptions. Therefore, this study aimed to assess the impact of GSPE administration on the liver oxidant system of healthy and diet-induced obese rats undergoing a sudden photoperiod shift. To this end, forty-eight photoperiod-sensitive Fischer 344/IcoCrl rats were fed either a standard (STD) or a cafeteria diet (CAF) for 6 weeks. A week before euthanizing, rats were abruptly transferred from a standard photoperiod of 12 h of light/day (L12) to either a short (6 h light/day, L6) or a long photoperiod (18 h light/day, L18) while receiving a daily oral dose of vehicle (VH) or GSPE (25 mg/kg). Alterations in body weight gain, serum and liver biochemical parameters, antioxidant gene and protein expression, and antioxidant metabolites were observed. Interestingly, GSPE partially ameliorated these effects by reducing the oxidative stress status in L6 through an increase in GPx1 expression and in hepatic antioxidant metabolites and in L18 by increasing the NRF2/KEAP1/ARE pathway, thereby showing potential in the treatment of circadian-related disorders by increasing the hepatic antioxidant response in a photoperiod-dependent manner.

Cryptic faults concern earthquake scientists, since they pose a hidden seismic potential which is hard to identify. To address this, the authors here study off-fault deformed geomorphic markers such as marine terraces using high-resolution LiDAR topography, optical dating of sediments and space geodetic observations.

A high priority of the World Health Organization (WHO) is the study of drugs against Pseudomonas aeruginosa, which has developed antibiotic resistance. In this order, recent research is analyzing biomaterials and metal oxide nanoparticles, such as chitosan (QT) and TiO2 (NT), which can transport molecules with biological activity against bacteria, to propose them as drug carrier candidates. In the present work, 10 modified benzofuran-isatin molecules were studied through computational simulation using density functional theory (DFT) and molecular docking assays against Hfq and LpxC (proteins of P. aeruginosa). The results show that the ligand efficiency of commercial drugs C-CP and C-AZI against Hfq is low compared with the best-designed molecule MOL-A. However, we highlight that the influence of NT promotes a better interaction of some molecules, where MOL-E generates a better interaction by 0.219 kcal/mol when NT is introduced in Hfq, forming the system Hfq-NT (Target-NT). Similar behavior is observed in the LpxC target, in which MOL-J is better at 0.072 kcal/mol. Finally, two pharmacophoric models for Hfq and LpxC implicate hydrophobic and aromatic-hydrophobic fragments.

Introduction Patients with systemic lupus erythematosus (SLE) have cognitive dysfunctions as a neuropsychiatric manifestation, associated with disabling symptoms. However, the presence of other medical or psychiatric comorbidities can delay or lead to a misdiagnose. Objectives To present a case of a patient with diagnostic difficulty in the face of multiple medical and neurocognitive comorbidities. Methods Description of a case report. Results 19-year-old female, Mexican, unemployed, with incomplete high school, with medical history of preterm birth by cesarean at 30 weeks due to placenta previa, history of early puberty, 4 years evolution of focal epilepsy, 1 year evolution of hypothyroidism and mild depression. She began her symptoms 4 years ago, characterized by an abrupt onset of memory disturbances, decreased concentration, poor academic performance, infantile behavior, need for affection, alternated with irritability periods, verbal and physical aggression, repetitive and erratic behavior. She went to multiple specialists with different therapeutic approaches without clinical improvement. In 2020, she was referred to our service for evaluation, evidenciating a mild depressive episode and psychotherapeutic treatment was started. Mental and neurological examination without alterations, normal vital signs, at physical examination: malar rash, oral ulcers, alopecia. Labs: increased erythrocyte sedimentation rate, normocytic anemia, leukopenia, rest normal. An electroencephalogram was requested, without alterations. Simple brain MRI was performed (Figure 1). Psychological (figure 2) and Neuropsychological tests (table 1) were performed, showing alterations in memory recall and inhibitory control. Due to the symptoms presented by the patient, SLE was suspected, and rheumatology evaluation was requested, integrating a diagnosis of incomplete SLE, and started treatment. The patient presented symptomatic improvement in cognitive symptoms and systemic signs. Likewise, a genetic evaluation was requested, without meeting the criteria for a genetic syndrome. The patient continues with symptomatic improvement and multidisciplinary treatment. Total scores Natural Normalized Diagnosis Orbitomedial 180 83 Mild alteration Pref-Anterior 22 106 Normal Dorsolateral 207 88 Normal BANFE total 409 104 Normal Image: Image 2: Conclusions Neurocognitive alterations are one of the most frequent manifestations of neurolupus, although its diagnosis and treatment may be delayed in the absence of clinical suspicion, mainly in multi-comorbid patients. In the case, the patient presented multiple diseases that can explain a picture of neurocognitive impairment, such as epilepsy, depression, hypothyroidism. However, in these cases, a multidisciplinary approach is imperative, requiring to rule out the different causes of the patient’s symptoms. Disclosure of Interest None Declared

Abstract Background The World Health Organization (WHO) provides protocols for the diagnosis of malaria. One of them is related to the staining process of blood samples to guarantee the correct parasite visualization. Ensuring the quality of the staining procedure on thick blood smears (TBS) is a difficult task, especially in rural centres, where there are factors that can affect the smear quality (e.g. types of reagents employed, place of sample preparation, among others). This work presents an analysis of an image-based approach to evaluate the coloration quality of the staining process of TBS used for malaria diagnosis. Methods According to the WHO, there are different coloration quality descriptors of smears. Among those, the background colour is one of the best indicators of how well the staining process was conducted. An image database with 420 images (corresponding to 42 TBS samples) was created for analysing and testing image-based algorithms to detect the quality of the coloration of TBS. Background segmentation techniques were explored (based on RGB and HSV colour spaces) to separate the background and foreground (leukocytes, platelets, parasites) information. Then, different features (PCA, correlation, Histograms, variance) were explored as image criteria of coloration quality on the extracted background information; and evaluated according to their capability to classify images as with Good or Bad coloration quality from TBS. Results For background segmentation, a thresholding-based approach in the SV components of the HSV colour space was selected. It provided robustness separating the background information independently of its coloration quality. On the other hand, as image criteria of coloration quality, among the 19 feature vectors explored, the best one corresponds to the 15-bins histogram of the Hue component with classification rates of > 97%. Conclusions An analysis of an image-based approach to describe the coloration quality of TBS was presented. It was demonstrated that if a robust background segmentation is conducted, the histogram of the H component from the HSV colour space is the best feature vector to discriminate the coloration quality of the smears. These results are the baseline for automating the estimation of the coloration quality, which has not been studied before, but that can be crucial for automating TBS’s analysis for assisting malaria diagnosis process.

Abstract The species Vigna unguiculata L. (Walp), commonly known as cowpea, is a multi-purpose legume that has been selected into three subspecies that are divided into grain, fodder and pod (yardlong bean) types. However, genetic bases for distinctions are not well understood. The purpose of this study was to apply genotyping-by-sequencing (GBS) and current reference genome for V. unguiculata to distinguish three subspecies and identify signatures of divergence. The collection of 130 accessions included 128 cultivated from: 1) ssp. cylindrica, fodder type; 2) ssp. sesquipedalis, pod vegetable type; and 3) ssp. unguiculata, grain type. Two wilds genotypes from spp. dekindtiana and spp. pubescens, were used to anchor phylogeny. A total of 11,083 highly informative single nucleotide polymorphisms (SNPs) were discovered. Wild accessions showed distinct genetic fingerprints and were separated from cultivated subspecies. Principal component analysis showed closer relationship between ssp. unguiculata and ssp. cylindrica compared to ssp. sesquipedalis. Relative differentiation of cultivated subspecies (with Fixation Index, F ST ) indicated the existence of discrete signatures of selection. This work clarifies the population structure, phylogeny, and domestication of cultivated cowpeas. Furthermore, significant genetic differences between grain and pod vegetable types can provide valuable information for future breeding in three cowpea groups.

The anticarcinogenic potential of a series of 1,5-disubstituted tetrazole-1,2,3-triazole hybrids (T-THs) was evaluated in the breast cancer (BC)-derived cell lines MCF-7 (ER+, PR+, and HER2−), CAMA-1 (ER+, PR+/−, and HER2−), SKBR-3 (ER+, PR+, and HER2+), and HCC1954 (ER+, PR+, and HER2+). The T-THs 7f, 7l, and 7g inhibited the proliferation of MCF-7 and CAMA-1, HCC1954, and SKBR-3 cells, respectively. The compounds with stronger effect in terms of migration and invasion inhibition were 7o, 7b, 7n, and 7k for the CAMA-1, MCF-7, HCC1954, and SKBR-3 cells respectively. Interestingly, these T-THs were the compounds with a fluorine present in their structures. To discover a possible target protein, a molecular docking analysis was performed for p53, p38, p58, and JNK1. The T-THs presented a higher affinity for p53, followed by JNK1, p58, and lastly p38. The best-predicted affinity for p53 showed interactions between the T-THs and both the DNA fragment and the protein. These results provide an opportunity for these compounds to be studied as potential drug candidates for breast cancer treatment.

Polyphenols play a key role in the modulation of circadian rhythms, while the cafeteria diet (CAF) is able to perturb the hepatic biological rhythm and induce important ROS production. Consequently, we aimed to elucidate whether grape seed proanthocyanidin extract (GSPE) administration recovers the CAF-induced hepatic antioxidant (AOX) misalignment and characterize the chronotherapeutic properties of GSPE. For this purpose, Fischer 344 rats were fed a standard diet (STD) or a CAF and concomitantly treated with GSPE at two time-points (ZT0 vs. ZT12). Animals were euthanized every 6 h and the diurnal rhythms of hepatic ROS-related biomarkers, hepatic metabolites, and AOX gene expression were examined. Interestingly, GSPE treatment was able to recover the diurnal rhythm lost due to the CAF. Moreover, GSPE treatment also increased the acrophase of Sod1, as well as bringing the peak closer to that of the STD group. GSPE also corrected some hepatic metabolites altered by the CAF. Importantly, the differences observed at ZT0 vs. ZT12 due to the time of GSPE administration highlight a chronotherapeutic profile on the proanthocyanin effect. Finally, GSPE could also reduce diet-induced hepatic oxidative stress not only by its ROS-scavenging properties but also by retraining the circadian rhythm of AOX enzymes.

Human-driven plant selection, a practice as ancient as agriculture itself, has laid the foundations of plant breeding and contemporary farming [...]

Leveraging innovative tools to speed up prebreeding and discovery of genotypic sources of adaptation from landraces, crop wild relatives, and orphan crops is a key prerequisite to accelerate genetic gain of abiotic stress tolerance in annual crops such as legumes and cereals, many of which are still orphan species despite advances in major row crops. Here, we review a novel, interdisciplinary approach to combine ecological climate data with evolutionary genomics under the paradigm of a new field of study: genome–environment associations (GEAs). We first exemplify how GEA utilizes in situ georeferencing from genotypically characterized, gene bank accessions to pinpoint genomic signatures of natural selection. We later discuss the necessity to update the current GEA models to predict both regional- and local- or micro-habitat–based adaptation with mechanistic ecophysiological climate indices and cutting-edge GWAS-type genetic association models. Furthermore, to account for polygenic evolutionary adaptation, we encourage the community to start gathering genomic estimated adaptive values (GEAVs) for genomic prediction (GP) and multi-dimensional machine learning (ML) models. The latter two should ideally be weighted by de novo GWAS-based GEA estimates and optimized for a scalable marker subset. We end the review by envisioning avenues to make adaptation inferences more robust through the merging of high-resolution data sources, such as environmental remote sensing and summary statistics of the genomic site frequency spectrum, with the epigenetic molecular functionality responsible for plastic inheritance in the wild. Ultimately, we believe that coupling evolutionary adaptive predictions with innovations in ecological genomics such as GEA will help capture hidden genetic adaptations to abiotic stresses based on crop germplasm resources to assist responses to climate change.“I shall endeavor to find out how nature’s forces act upon one another, and in what manner the geographic environment exerts its influence on animals and plants. In short, I must find out about the harmony in nature” Alexander von Humboldt—Letter to Karl Freiesleben, June 1799.

Abstract Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.

With the increasing negative impacts on worldwide food production caused by pests, the recovery of native entomopathogenic nematodes (EPNs) is relevant, since they are adapted to local environments, entomofauna, and significant virulence. Therefore, the present study was designed to recover and understand the phylogenetic diversity of EPNs and their associated bacterial endosymbionts, from banana and plantain crops, as alternatives for the control of weevil species. An extensive sampling of western Colombia covered 325 ha, yielding the recovery of three EPNs’ isolates (0.49% of the samples). The molecular characterization included four mitochondrial and nuclear loci, which, after merging with the sequences of 48 species, confirmed the presence of Steinernema carpocapsae, the first report of S. costaricense in South America, and monophyly in most of the Steinernema clades. The tree topologies were consistent for the nuclear loci but not for mitochondrial, probably due to the high nucleotide substitution rate, deficit in the number of species available for these loci, and incomplete lineage sorting. The endosymbiotic bacteria associated with S. carpocapsae were identified as Xenorhabdus nematophila. However, the S. costaricense bacterial symbiont presented a genetic similarity to X. koppenhoeferi and X. khoisanae, which are still uncertain in their classification. The identification of S. costaricense in South America indicates the wide range distribution of this species in the Americas and its ability to persist in different soil types. For the first time, EPN isolation and phylogenetic characterization are directed to plantain and banana crops. Leveraging EPNs’ diversity promises novel applications for crop protection, while the genetic resources from the bacterial endosymbionts may provide metabolites with a wide spectrum of uses, either for agricultural or medicinal purposes.

Assessing interspecific adaptive genetic variation across environmental gradients offers insight into the scale of habitat-dependent heritable heterotic effects, which may ultimately enable pre-breeding for abiotic stress tolerance and novel climates. However, environmentally dependent allelic effects are often bypassed by intra-specific single-locality genome-wide associations studies (GWAS). Therefore, in order to bridge this gap, this study aimed at coupling an advanced panel of drought/heat susceptible common bean (Phaseolus vulgaris L.) × tolerant tepary bean (P. acutifolius A. Gray) interspecific lines with last-generation multi-environment GWAS algorithms to identify novel sources of heat and drought tolerance to the humid and dry subregions of the Caribbean coast of Colombia, where the common bean typically exhibits maladaptation to extreme weather. A total of 87 advanced lines with interspecific ancestries were genotyped by sequencing (GBS), leading to the discovery of 15,645 single-nucleotide polymorphism (SNP) markers. Five yield traits were recorded for each genotype and inputted in modern GWAS algorithms (i.e., FarmCPU and BLINK) to identify the putative associated loci across four localities in coastal Colombia. Best-fit models revealed 47 significant quantitative trait nucleotides (QTNs) distributed in all 11 common bean chromosomes. A total of 90 flanking candidate genes were identified using 1-kb genomic windows centered in each associated SNP marker. Pathway-enriched analyses were done using the mapped output of the GWAS for each yield trait. Some genes were directly linked to the drought tolerance response; morphological, physiological, and metabolic regulation; signal transduction; and fatty acid and phospholipid metabolism. We conclude that habitat-dependent interspecific polygenic effects are likely sufficient to boost common bean adaptation to the severe climate in coastal Colombia via introgression breeding. Environmental-dependent polygenic adaptation may be due to contrasting levels of selection and the deleterious load across localities. This work offers putative associated loci for marker-assisted and genomic selection targeting the common bean’s neo-tropical lowland adaptation to drought and heat.

The growing human population and climate change are imposing unprecedented challenges on the global food supply [...]

Abstract The magnetotelluric method is increasingly being used to monitor electrical resistivity changes in the subsurface. One of the preferred parameters derived from the surface impedance is the strike direction, which is very sensitive to changes in the direction of the subsurface electrical current flow. The preferred method for estimating the strike changes is that provided by the phase tensor because it is immune to galvanic distortions. However, it is also a fact that the associated analytic formula is unstable for noisy data, something that limits its applicability for monitoring purposes, because in general this involves comparison of two or more very similar datasets. One of the issues is that the noise complicates the distribution of estimates between the four quadrants. This can be handled by sending all values to the same quadrant by adding or subtracting the appropriate amount. This is justified by showing that the analytic formula is also a least squares solution. This is equivalent to define penalty functions for the matrix of eigenvalues and then select the minima numerically. Contrary to the analytic formula, this numerical approach can be generalized to compute strikes using windows of any number of periods, thus providing tradeoffs between variance and resolution. The performance of the proposed approach is illustrated by its application to synthetic data and to real data from a monitoring array in the Cerro Prieto geothermal field, México.

Grafting induces precocity and maintains clonal integrity in fruit tree crops. However, the complex rootstock × scion interaction often precludes understanding how the tree phenotype is shaped, limiting the potential to select optimum rootstocks. Therefore, it is necessary to assess (1) how seedling progenies inherit trait variation from elite ‘plus trees’, and (2) whether such family superiority may be transferred after grafting to the clonal scion. To bridge this gap, we quantified additive genetic parameters (i.e., narrow sense heritability—h2, and genetic-estimated breeding values—GEBVs) across landraces, “criollo”, “plus trees” of the super-food fruit tree crop avocado (Persea americana Mill.), and their open-pollinated (OP) half-sib seedling families. Specifically, we used a genomic best linear unbiased prediction (G-BLUP) model to merge phenotypic characterization of 17 morpho-agronomic traits with genetic screening of 13 highly polymorphic SSR markers in a diverse panel of 104 avocado “criollo” “plus trees.” Estimated additive genetic parameters were validated at a 5-year-old common garden trial (i.e., provenance test), in which 22 OP half-sib seedlings from 82 elite “plus trees” served as rootstocks for the cv. Hass clone. Heritability (h2) scores in the “criollo” “plus trees” ranged from 0.28 to 0.51. The highest h2 values were observed for ribbed petiole and adaxial veins with 0.47 (CI 95%0.2–0.8) and 0.51 (CI 0.2–0.8), respectively. The h2 scores for the agronomic traits ranged from 0.34 (CI 0.2–0.6) to 0.39 (CI 0.2–0.6) for seed weight, fruit weight, and total volume, respectively. When inspecting yield variation across 5-year-old grafted avocado cv. Hass trees with elite OP half-sib seedling rootstocks, the traits total number of fruits and fruits’ weight, respectively, exhibited h2 scores of 0.36 (± 0.23) and 0.11 (± 0.09). Our results indicate that elite “criollo” “plus trees” may serve as promissory donors of seedling rootstocks for avocado cv. Hass orchards due to the inheritance of their outstanding trait values. This reinforces the feasibility to leverage natural variation from “plus trees” via OP half-sib seedling rootstock families. By jointly estimating half-sib family effects and rootstock-mediated heritability, this study promises boosting seedling rootstock breeding programs, while better discerning the consequences of grafting in fruit tree crops.

Grafting typically offers a shortcut to breed tree orchards throughout a multidimensional space of traits. Despite an overwhelming spectrum of rootstock-mediated effects on scion traits observed across several species, the exact nature and mechanisms underlying the rootstock-mediated effects on scion traits in cacao (Theobroma cacao L.) plants often remain overlooked. Therefore, we aimed to explicitly quantify rootstock-mediated genetic contributions in recombinant juvenile cacao plants across target traits, specifically cadmium (Cd) uptake, and its correlation with growth and physiological traits. Content of chloroplast pigments, fluorescence of chlorophyll a, leaf gas exchange, nutrient uptake, and plant biomass were examined across ungrafted saplings and target rootstock × scion combinations in soils with contrasting levels of Cd. This panel considered a total of 320 progenies from open-pollinated half-sib families and reciprocal full-sib progenies (derived from controlled crosses between the reference genotypes IMC67 and PA121). Both family types were used as rootstocks in grafts with two commercial clones (ICS95 and CCN51) commonly grown in Colombia. A pedigree-based best linear unbiased prediction (A-BLUP) mixed model was implemented to quantify rootstock-mediated narrow-sense heritability (h2) for target traits. A Cd effect measured on rootstocks before grafting was observed in plant biomass, nutrient uptake, and content of chloroplast pigments. After grafting, damage to the Photosystem II (PSII) was also evident in some rootstock × scion combinations. Differences in the specific combining ability for Cd uptake were mostly detected in ungrafted rootstocks, or 2 months after grafting with the clonal CCN51 scion. Moderate rootstock effects (h2> 0.1) were detected before grafting for five growth traits, four nutrient uptake properties, and chlorophylls and carotenoids content (h2 = 0.19, 95% CI 0.05–0.61, r = 0.7). Such rootstock effects faded (h2< 0.1) when rootstock genotypes were examined in soils without Cd, or 4 months after grafting. These results suggest a pervasive genetic conflict between the rootstock and the scion genotypes, involving the triple rootstock × scion × soil interaction when it refers to Cd and nutrient uptake, early growth, and photosynthetic process in juvenile cacao plants. Overall, deepening on these findings will harness early breeding schemes of cacao rootstock genotypes compatible with commercial clonal scions and adapted to soils enriched with toxic levels of Cd.

A semisynthesis of 6β-acetoxyvouacapane-1,5-disusbtituted tetrazoles derivatives from the leaves of Caesalpinia platyloba by using the Ugi-azide multicomponent reaction as a key step reaction is described. To our knowledge, this is the first report where a non-natural product such as 1,5-disusbtituted tetrazole has been linked to a natural product or derivate of a natural product, and beyond the biological relevance that the target molecules present, this work contributes to the area of natural products as well as multicomponent reactions.

Seed uniformity and stability testing, and multiplication, are key steps in the seed supply chain of the common bean (Phaseolus vulgaris L.) and other crops. Optimizing agronomical practices in these phases can ultimately ensure seed quality and availability, and germplasm prospective utilization. However, farmers have rarely standardized seed testing and propagation protocols in local common bean landraces conserved in situ. An example of this is the Liborino variety (var.), a promising yellow Andean common bean known for its presumably high digestibility and adaptation to the local conditions of the Cauca river canyon (northwest Andes of Colombia), but likely experiencing genetic erosion after decades of suboptimal propagation. Therefore, this work intended to evaluate and select locally adapted genotypes of common bean var. Liborino for commercial use, to be later multiplied, evaluated by participatory breeding, and eventually shared with farmers. Specifically, we evaluated 44 accessions of var. Liborino common bean in six adaption and yield field trials in the Cauca river canyon at 1100 and 1400 m a.s.l, and in AGROSAVIA’s “La Selva” research station at 2100 m a.s.l. In parallel, we carried out standardized seed multiplication of a Liborino genotype using best practices to guarantee uniformity and stability. From the 44 accessions, nine were well adapted to the tested local conditions. Four of these accessions exhibited a bush type growth habit, while the remaining five were climbers. The trials revealed maximum average extrapolated yields of up to 1169.4 ± 228.4 kg ha−1 for the bush types (G8152) and up to 1720.0 ± 588.4 kg ha−1 for the climbers (G51018), both at 2100 m a.s.l. Three climbing accessions matched farmers’ expectations for seed coat color and shape, according to a participatory selection exercise. Uniform and stable seed of the selected genotype was delivered in 2022 to 39 farmers, ~6.5 kg of seeds per farmer. Our results will allow implementing bean genetic improvement pipelines, promoting var. Liborino commercialization, and boosting the economic and sustainable development of the rural communities in the Cauca river canyon. Seed uniformity testing and multiplication pipelines must be extended to other bean landraces conserved in situ.

This paper seeks to offer an update of the syntactic representation of adverbials in the Lexical Constructional Model and the multipurpose lexico-conceptual knowledge base, FunGramKB, and to implement the conditions that are necessary for an effective parsing of such constituents within ARTEMIS, a NLP prototype within FunGramKB for the computational treatment of the syntax and semantics of sentences. As regards the status of adverbials in the Layered Structure of the Clause (LSC) proposed in Role and Reference Grammar, it is striking that they have been somewhat sidelined, despite the programmatic proposal in Van Valin (2005) for a distribution of adjuncts along the different layers in the LSC. Since then, almost no further contribution has been offered to fully expand this new scheme. Thus, our aim is to fully embody a layered approach for adverbials and to adapt our proposal to the conditions imposed by the Grammar Development Environment in ARTEMIS, by developing the rules that are necessary for the parsing of the catalogue of adverbials of a corpus written in the controlled natural language ASD-STE100.

Legionella spp. are microorganisms that are generally found in the aquatic environment (rivers, streams, lakes, among others). The importance in public health is in the fact that this bacterium is capable of multiplying and propagating in artificial aquatic systems (piping systems, storage tanks, fountains, and cooling towers), giving rise to diseases in humans called legionellosis, transmitted by inhalation of contaminated water droplets or aerosols and whose complications can lead to the death of the patient. Legionellosis is of worldwide distribution, Legionella pneumophila being the most commonly involved species in outbreaks and reported cases. The people most at risk are the elderly, people with weakened immune systems, and people with a history of smoking. Around the world, regulatory agencies and health organizations have issued and established recommendations with the purpose of controlling and preventing the risk of contracting this disease, which include the sanitation of water supplies, maintenance through regular cleaning and disinfection of facilities and devices for reducing the presence of this pathogen. The main objective of this review is to present in a general manner, aspects related to the disease known as legionellosis, its casual agents, habitat, transmission form, and phenotypic and metabolic characteristics. Likewise, the methods of control and prevention of these pathogens are presented, including a potential biotechnological alternative that can contribute to actions in favour of the protection of public health through the use of compounds with surface activity called biosurfactants.

Single nucleotide polymorphism (SNP) markers have multiple applications in plant breeding of small grains. They are used for the selection of divergent parents, the identification of genetic variants and marker-assisted selection. However, the use of SNPs in varietal purity assessment is under-reported, especially for multi-line varieties from the public sector. In the case of variety evaluation, these genetic markers are tools for maintaining varietal distinctness, uniformity and stability needed for cultivar release of multi-line or pure-line varieties of inbred crops. The objective of this research was to evaluate the purity and relationships of one original (AV-25) and two multi-line sub-populations (AV25-T and AV25-S) of the inbreeding species, oats (Avena sativa L.). Both sub-populations could be useful as forages in the central highland region of Colombia (>2000 masl), such as in the departments of Boyacá and Cundinamarca, even though they were derived from an original composite mixture widely used in the mountainsides of the southern department of Nariño named Avena 25. Representative single plant selections (SPS) from the two sub-populations were grown together with SPS harvests from off-type plants (early and late) and plants from the original AV25 composite mixture, to determine their genetic similarity. Plants were genotyped by DNA extraction of a plateful of 96 individual plant samples and SNPs were detected for an Illumina Infinium 6K Chip assay. The data were used for the analysis of genetic structure and population relationships. The grouping observed based on the genetic data indicated that AV25-T and AV25-S were homogeneous populations and somewhat divergent in their genetic profile compared to the original AV25-C mix. In addition, to the two commercial, certified oat varieties (Cajicá and Cayuse) were different from these. The early and late selections were probable contaminants and could be discarded. We concluded that the use of SNP markers is an appropriate tool for ensuring genetic purity of oat varieties.

Grafting is typically utilized to merge adapted seedling rootstocks with highly productive clonal scions. This process implies the interaction of multiple genomes to produce a unique tree phenotype. However, the interconnection of both genotypes obscures individual contributions to phenotypic variation (rootstock-mediated heritability), hampering tree breeding. Therefore, our goal was to quantify the inheritance of seedling rootstock effects on scion traits using avocado (Persea americana Mill.) cv. Hass as a model fruit tree. We characterized 240 diverse rootstocks from 8 avocado cv. Hass orchards with similar management in three regions of the province of Antioquia, northwest Andes of Colombia, using 13 microsatellite markers simple sequence repeats (SSRs). Parallel to this, we recorded 20 phenotypic traits (including morphological, biomass/reproductive, and fruit yield and quality traits) in the scions for 3 years (2015–2017). Relatedness among rootstocks was inferred through the genetic markers and inputted in a “genetic prediction” model to calculate narrow-sense heritabilities (h2) on scion traits. We used three different randomization tests to highlight traits with consistently significant heritability estimates. This strategy allowed us to capture five traits with significant heritability values that ranged from 0.33 to 0.45 and model fits (r) that oscillated between 0.58 and 0.73 across orchards. The results showed significance in the rootstock effects for four complex harvest and quality traits (i.e., total number of fruits, number of fruits with exportation quality, and number of fruits discarded because of low weight or thrips damage), whereas the only morphological trait that had a significant heritability value was overall trunk height (an emergent property of the rootstock–scion interaction). These findings suggest the inheritance of rootstock effects, beyond root phenotype, on a surprisingly wide spectrum of scion traits in “Hass” avocado. They also reinforce the utility of polymorphic SSRs for relatedness reconstruction and genetic prediction of complex traits. This research is, up to date, the most cohesive evidence of narrow-sense inheritance of rootstock effects in a tropical fruit tree crop. Ultimately, our work highlights the importance of considering the rootstock–scion interaction to broaden the genetic basis of fruit tree breeding programs while enhancing our understanding of the consequences of grafting.

Mint (Mentha L., Lamiaceae) is a strongly scented herb of the family Lamiaceae that is grown mostly by clonal propagation, making it a valuable species for the study of somaclonal variation and its phenotypic consequences. The recent introduction of a few species of mint in South America, followed by a presumably rampant propagation, make this region particularly ideal for studying the extent of somaclonal genetic diversity. Hence, the objective of this work was to offer a preliminary characterization of somaclonal genetically coding diversity of the mint in the northern Andes in order to address the question of whether somaclonal variants may have emerged despite relatively recent introductions in a region where mint is not native. A total of 29 clonally propagated specimens, collected in mint export farms in the province of Antioquia, a major region for mint production in the northwest Andes of Colombia, were genotyped using RNA sequencing (RNA-Seq). SNP calling was carried out from the leaves’ transcriptome profiles of each plant by combining the GATK4 and TRINITY protocols, obtaining a total of 2033 loci across 912 transcripts with a minimum read depth of 20X and 4% of missing data. Unsupervised machine learning algorithms considered the K-means, AGNES and UPGMA approaches, all of which suggested three genetic clusters for M. spicata and a unique cluster for M. × piperita. The results indicate that at least two different origins of M. spicata reached the eastern region of the Antioquia province, clonally propagated in the locality ever since for local consumption and export. One of these ancestries had more population structure, possibly due to environmental or anthropological pressures that intervened in the fragmentation of this genetic group or to a higher somaclonal mutation rate. This work offers a first step into the study of the accumulation and transmission of presumably quasi-neutral somatic mutations at coding regions in an herbaceous clonally propagated scented species such as mint, likely favored by an expected population expansion after its Andean introduction. These ad hoc hypotheses warrant further study as part of future research.

Studying the genetics of adaptation to new environments in ecologically and industrially important tree species is currently a major research line in the fields of plant science and genetic improvement for tolerance to abiotic stress. Specifically, exploring the genomic basis of local adaptation is imperative for assessing the conditions under which trees will successfully adapt in situ to global climate change. However, this knowledge has scarcely been used in conservation and forest tree improvement because woody perennials face major research limitations such as their outcrossing reproductive systems, long juvenile phase, and huge genome sizes. Therefore, in this review we discuss predictive genomic approaches that promise increasing adaptive selection accuracy and shortening generation intervals. They may also assist the detection of novel allelic variants from tree germplasm, and disclose the genomic potential of adaptation to different environments. For instance, natural populations of tree species invite using tools from the population genomics field to study the signatures of local adaptation. Conventional genetic markers and whole genome sequencing both help identifying genes and markers that diverge between local populations more than expected under neutrality, and that exhibit unique signatures of diversity indicative of “selective sweeps.” Ultimately, these efforts inform the conservation and breeding status capable of pivoting forest health, ecosystem services, and sustainable production. Key long-term perspectives include understanding how trees’ phylogeographic history may affect the adaptive relevant genetic variation available for adaptation to environmental change. Encouraging “big data” approaches (machine learning—ML) capable of comprehensively merging heterogeneous genomic and ecological datasets is becoming imperative, too.

Molecular evolution offers an insightful theory to interpret the genomic consequences of thermal adaptation to previous events of climate change beyond range shifts. However, disentangling often mixed footprints of selective and demographic processes from those due to lineage sorting, recombination rate variation, and genomic constrains is not trivial. Therefore, here we condense current and historical population genomic tools to study thermal adaptation and outline key developments (genomic prediction, machine learning) that might assist their utilization for improving forecasts of populations’ responses to thermal variation. We start by summarizing how recent thermal-driven selective and demographic responses can be inferred by coalescent methods and in turn how quantitative genetic theory offers suitable multi-trait predictions over a few generations via the breeder’s equation. We later assume that enough generations have passed as to display genomic signatures of divergent selection to thermal variation and describe how these footprints can be reconstructed using genome-wide association and selection scans or, alternatively, may be used for forward prediction over multiple generations under an infinitesimal genomic prediction model. Finally, we move deeper in time to comprehend the genomic consequences of thermal shifts at an evolutionary time scale by relying on phylogeographic approaches that allow for reticulate evolution and ecological parapatric speciation, and end by envisioning the potential of modern machine learning techniques to better inform long-term predictions. We conclude that foreseeing future thermal adaptive responses requires bridging the multiple spatial scales of historical and predictive environmental change research under modern cohesive approaches such as genomic prediction and machine learning frameworks.

Some of the largest impacts of climate change are expected in the environmentally heterogeneous and species rich high mountain ecosystems. Among those, the Neotropical alpine grassland above the tree line (c. 2,800 m), known as Páramo, is the fastest evolving biodiversity hotspot on earth, and one of the most threatened. Yet, predicting climate responses of typically slow-growing, long-lived plant linages in this unique high mountain ecosystem remains challenging. Here we coupled climate sensitivity modeling and adaptive potential inferences to efficiently assess climate vulnerability of Espeletia, Páramo’s most iconic, predominant and rapidly evolving plant complex. In order to estimate climate sensitivity, we first modeled the distribution of 28 Espeletia taxa under a niche conservatism scenario using altitude and five current (1970–2000) and future (2050 RCP 8.5) bioclimatic variables across 36 different Páramo complexes in the northern Andes (49% of the world’s Páramo area). As an alternative to range shifts via migration, we also computed the adaptive capacity of these Páramo complexes by considering three enhancing factors of the biodiversity’s adaptive potential as well as three environmental limiting factors of the populations’ plastic response. These predictors showed that diverse Páramos in the Eastern Cordillera were more vulnerable likely because the counteracting effects of the adaptive potential (r = −0.93 ± 0.01) were not sufficient to buffer higher distribution losses (r = 0.39 ± 0.01). Agriculture (r = −0.48 ± 0.01), mining (r = −0.36 ± 0.01), and rural population density (r = −0.23 ± 0.01) also weakened the adaptive capacity. These results speak for a limited persistence via migration in the short-term responses of Espeletia to climate change, even though the past population dynamics in concert with glacial cycling is indicative of a predominant role of range shifts. Furthermore, changing climate, together with a general inability to adapt, may eventually constrain the rapid diversification in the Espeletia complex. Our integrative modeling illustrates how future climate may impact plant populations in a mega diverse and highly threatened ecosystem such as the Páramo, and encourages carrying out similar estimates in diverse plant complexes across other high mountain and island-like ecosystems.

Direct democracy (DD) – including initiatives and referendums – is increasingly used by citizens and governments to establish new policies around the world. Although framed as a tool that benefits citizens, it is also common for government actors, including parties, to utilise DD in initiating and pushing through new policies. To explain this puzzling development, existing research examines the regulative design of DD. Going a step further, this article explains how the design of DD originates. Using process tracing methodology, I examine the case of Mexico – the most recent adopter of DD in 2014 – and illustrate how, when, and how DD can be used and modified. I argue that DD is endogenous: we cannot conceive of it independently of the political forces that generated it. Other prominent cases, such as Uruguay, suggest that DD was adopted to pursue party goals or to shape a particular government structure. Legislatures certainly provide the masses the option of engaging in DD but they do so on their own terms.

In regard to the actual public health global emergency and, based on the state of the art about the ways to inhibit the SARS-CoV-2 treating the COVID19, a family of 1,5-disubstituted tetrazole-1,2,3-triazoles, previously synthesized, have been evaluated through in silico assays against the main protease of the mentioned virus (CoV-2-MPro). The results show that three of these compounds present a more favorable interaction with the selected target than the co-crystallized molecule, which is a peptide-like derivative. It was also found that also hydrophobic interactions play a key role in the ligand-target molecular couplings, due to the higher hydrophobic surfaces into the active site. Finally, a pharmacophore model has been proposed based on the results below, and a family of 1,5-DT derivatives has been designed and tested with the same methods employed in this work. It was concluded that the compound with the isatin as a substituent (P8) present the higher ligand-target interaction, which makes this a strong drug candidate against COVID19, due can inhibit the CoV-2-MPro protein.