Biology subjects

Lopez, M. E.

Publications and source records attributed to Lopez, M. E..

12 recordsLinked to original sources

bioRxiv2026

ST6Gal2 promotes α2,6-sialylation and aggressive phenotypes in neuroblastoma cells

Neuroblastoma is the most common extracranial solid tumor of childhood. Its clinical behavior ranges from spontaneous regression to lethal, treatment-refractory disease. Aberrant 2,6-sialylation contributes to aggressive phenotypes in many cancers, but the role of ST6Gal2, a neural-enriched 2,6-sialyltransferase, in neuroblastoma is largely unexplored. Here, we examine the clinical and functional significance of ST6Gal2 in neuroblastoma. In two independent public cohorts (SEQC, n=498; Kocak, n=649), high ST6GAL2 expression was associated with significantly worse overall and event-free survival. In the SEQC cohort, ST6GAL2 expression was higher in high-risk and MYCN-amplified tumors, varied across International Neuroblastoma Staging System stages, and correlated positively with a mesenchymal transcriptional signature (Spearman {rho}=0.181). The mesenchymal correlation was reproduced in the Kocak cohort ({rho}=0.204). Stable shRNA-mediated knockdown of ST6GAL2 in SK-N-AS and SK-N-BE(2) cells reduced proliferation and viability, impaired wound closure, and decreased migration and invasion. In preliminary experiments in SK-N-AS cells, ST6GAL2 knockdown reduced binding of Sambucus nigra agglutinin, consistent with a role for ST6Gal2 in 2,6-sialylation. Together, these findings link ST6Gal2 expression to aggressive clinical and transcriptional features and pro-tumorigenic phenotypes in neuroblastoma and nominate ST6Gal2-mediated sialylation as a candidate pathway for mechanistic study.

cancer biology↗

bioRxiv2025

DNA extracted from boiled archival fish bones yields high quality whole genome sequencing data

Archival samples provide a unique source of DNA, offering the potential to extend the temporal scale of genetic studies by decades to centuries. Fish hard structures, such as otoliths and scales, serve as records for fish collected during fisheries monitoring across a large spatiotemporal scale. Operculum bones are a type of fish hard structure that, although less commonly collected, have been utilized in genetic studies. However, the usefulness of archived operculum bones to provide high quality whole genome sequence information has not been thoroughly evaluated. Here, we applied a commercially available extraction protocol, with minor adjustments, to isolate genomic DNA from operculum bones of Eurasian perch collected up to 47 years ago, followed by standard short-read whole genome sequencing. By comparing the metrics of DNA and whole genome sequencing data of bones with contemporary muscle samples, we demonstrate that the application of a simple extraction protocol on boiled archival fish operculum bones yields high quality genomic information that is comparable to fresh tissue, highlighting the role of archival operculum bones as an overlooked repository of valuable genomic information.

molecular biology↗

bioRxiv2024

The contrasting flowering-time among coffee genotypes is associated with ectopic and differential expressions of genes related to environment, floral development, and hormonal regulation

The molecular pathways underlying floral activation and development are well described in model species, but exhibit significant diversity in plants that is poorly understood in crops with complex cycles, such as Coffea arabica L. The reproductive development of coffee plants is biannual, and the flowering time is crucial for the coffee productivity and cup quality. In this study, we explored the plasticity of floral development and flowering-time of contrasting coffee genotypes to understand the associated metabolic and regulatory transcriptional profiles. Firstly, we compared the reproductive development of three coffee genotypes, confirming that Acaua is late flowering, Oeiras is early flowering, and the natural mutant Semperflorens (Sf) exhibits continuous flowering throughout the year. Analysis of sugar and ethylene content revealed quantitative differences between genotypes in both leaves and floral buds. To associate these phenotypic differences with the regulatory developmental pathways, we performed RNA-seq analysis comparing the shoot apical meristems, floral buds and leaves of different genotypes. Our analysis identified 12.478 differentially expressed genes, which showed enriched terms mainly related to hormonal regulation, external stimulus and floral development. Notably, some major players of reproductive development, as homologs of FLOWERING LOCUS T and MADS-box genes, showed contrasting expression patterns, generally being ectopically upregulated in the Sf mutant. These findings were associated with the phenotypic differences among coffee genotypes. In conclusion, the present study improves the understanding of the divergence of floral development in coffee, providing valuable insights for directing breeding programs and future studies aiming at controlling floral development and enhancing crop production.

plant biology↗

bioRxiv2023

Epigenetic and transcriptional landscape of heat-stress memory in woodland strawberry (Fragaria vesca)

We have previously reported that different stresses can lead to substantial DNA methylation changes in strawberry. Here, we wanted to assess the heritability of heat-stress induced DNA methylation and transcriptional changes following asexual and sexual reproduction in a plant. Woodland strawberry (Fragaria vesca) is an ideal model to study epigenetic inheritance in plants because it presents two modes of reproduction: sexual and asexual. Here we wanted to assess if heat-stress induced DNA methylation changes can be transmitted via asexual reproduction and whether past stresses can also affect sexually propagated progenies. Our genome-wide study provides evidence for a memory acquisition and maintenance in F. vesca. We found that certain DNA methylation changes can stably be transmitted over at least three asexual generations. Finally, the first sexual generation by selfing from stressed maternal and their respective non-stressed asexual daughter plants showed both shared and unique stress responses. This suggests that an acquired molecular memory from the previous heat-stress event was transmitted. This molecular memory might be involved in functional plasticity and stress adaption, an important aspects that will have to be investigated in future studies. Finally, these findings may contribute to novel approaches that may contribute to the breeding of climate-ready plants. IN A NUTSHELLO_ST_ABSBackgroundC_ST_ABSWith ongoing climate change, natural plant populations and crops are facing stress situations more frequently and at higher intensity. These unfavorable growing conditions force plants to develop strategies to adapt to persist. One of these strategies involves epigenetic mechanisms which can affect the activity of genes without altering the actual DNA sequence. These molecular modifications can be retained by plants as a molecular "memory" which might be used later to better respond to a stressful event. QuestionIs there multi-generational persistence of heat-stress induced epigenetic patterns in strawberry and are heritable epigenetic changes associated with stress adaptation? FindingsWe found that the strawberry methylome and transcriptome respond with a high level of flexibility to heat-stress. In addition, we took advantage of the two reproductive modes of strawberry (asexual and sexual) to evaluate the acquisition and maintenance of molecular stress memory. We showed how specific DNA methylation and gene expression changes can persist for a long time in progeny plants. We found that the asexual, and seemingly also sexual progenies can retain information in the genome of a past stressful condition that was encountered by its progenitor. Next stepsOur work presents valuable epigenetic and transcriptional screening data to understand plant memory maintenance and transmission over generations. The most important next step will be to assess if heritable stress-induced epigenetic changes can contribute to stress adaptation through a plant competition experiment in natural environments. One sentence summaryStrawberry can transmit molecular stress-memory at the DNA methylation and transcriptional level over multiple generations which may play an important role in stress adaptation.

plant biology↗

bioRxiv2021

Crosstalk between Ethylene and ABA during changes in soil water content reveals a role of ACC in coffee anthesis regulation

O_LICoffee (Coffea arabica L.) presents an asynchronous flowering regulated by endogenous and environmental stimulus, and anthesis occurs once plants are rehydrated after a period of water deficit. C_LIO_LIWe evaluated the evolution of Abscisic Acid (ABA), ethylene, 1-aminocyclopropane-1-carboxylate (ACC) content, ACC oxidase (ACO) activity, and expression analysis of the Lysine Histidine Transporter 1 (LHT1) transporter, in roots, leaves and, flower buds from three coffee genotypes (Coffea arabica L. cv Oeiras, Acaua, and Semperflorens) cultivated under field conditions with two experiments. In a third field experiment, the effect of exogenous supply of ACC in coffee anthesis was evaluated. C_LIO_LIWe found an increased ACC level in all tissues from the three coffee genotypes in the re-watering period just before anthesis for all tissues and high expression of the LHT1 gene in flower buds and leaves. Ethylene content and ACO activity decreased from rainy to dry period whereas ABA content increased. Higher number of opened and G6 stage flower buds were observed in the treatment with exogenous ACC. C_LIO_LIThe results showed that the interaction of ABA-ACO-ethylene and intercellular ACC transport among leaves, buds, and roots in coffee favors an increased level of ACC that is most likely, involved as a modulator in coffee anthesis. C_LI

plant biology↗

bioRxiv2019

Cluster-permutation statistical analysis for high-dimensional brain-wide functional connectivity mapping

Brain functional connectivity (FC) analyses based on magnetoencephalographic (MEG) signals have yet to exploit the intrinsic high-dimensional information. Typically, these analyses are constrained to regions of interest to avoid the curse of dimensionality, which leads to conservative hypothesis testing. We removed such constraint by extending cluster-permutation statistics for high-dimensional MEG-FC analyses. We demonstrated the feasibility of this approach by identifying MEG-FC resting-state changes in mild cognitive impairment (MCI), a prodromal stage of Alzheimers disease. We found dense clusters of increased connectivity strength in MCI compared to healthy controls (hypersynchronization), in delta (1-4 Hz) and higher-theta (6-8 Hz) bands oscillations. These clusters mainly consisted of interactions between occipitofrontal and occipitotemporal regions in the left hemisphere and could potentially be used as neuromarkers of early progression in Alzheimers disease. Our novel approach can be used to generate high-resolution statistical FC maps for neuroimaging studies in general.

neuroscience↗

bioRxiv2019

Whole genome re-sequencing reveals recent signatures of selection in three strains of farmed Nile tilapia (Oreochromis niloticus)

Nile tilapia (Oreochromis niloticus Linnaeus, 1758) belong to the second most cultivated group of fish in the world, mainly because of its favorable characteristics for production. Genetic improvement programs in this species began in the late 1980s to enhance some traits of commercial interest. The resulting domestication process of Nile tilapia may have modified the genome through selective pressure, leaving signals that can be detected at the molecular level. In this work, signatures of selection were identified using genome-wide SNP data, using two complementary methods based in extended haplotype homozygosity (EHH)._Whole-genome sequencing of 326 individuals from three strains (A, B and C) of farmed tilapia from two countries (Brazil and Costa Rica) was carried out using Illumina HiSeq 2500 technology. After applying conventional SNP-calling and quality-control pipelines, a total of ~1.3M high-quality SNPs were inferred and used as input for the Integrated Haplotype Score (|iHS|) and standardized log-ratio of integrated EHH between pairs of populations (Rsb) methods. We detected 16, 174 and 96 candidate genes subjected to selection in strain A, B, and C, respectively. These candidate genes represent putative genomic landmarks that could contain functions of biological and commercial interest.

genomics↗

bioRxiv2019

High-throughput single nucleotide polymorphism (SNP) discovery and validation through whole-genome resequencing of hundreds of individuals in Nile tilapia (Oreochromis niloticus)

Nile Tilapia (Oreochromis niloticus) is the second most important farmed fish in the world and a sustainable source of protein for human consumption. Several genetic improvement programs have been established for this species in the world and so far, they are mainly based on conventional selection using genealogical and phenotypic information to estimate the genetic merit of breeders and make selection decisions. Genome-wide information can be exploited to efficiently incorporate traits that are difficult to measure in the breeding goal. Thus, SNPs are required to investigate phenotype-genotype associations and determine the genomic basis of economically important traits. We performed de novo SNP discovery in three different populations of farmed tilapias. A total of 29.9 million non-redundant SNPs were identified through Illumina (HiSeq 2500) whole-genome resequencing of 326 individual samples. After applying several filtering steps including removing SNP based on genotype and site quality, presence of Mendelian errors, and non unique position in the genome, a total of high quality 50,000 SNP were selected for validation purposes. These SNPs were highly informative in the three populations analyzed showing between 43,869 (94%) and 46,139 (99%) SNP in HWE; 37,843 (76%) and 45,171(90%) SNP with a MAF higher than 0.05 and; 43,450 (87%) and 46,570 (93%) SNPs with a MAF higher than 0.01. The final list of 50K SNPs will be very useful for the dissection of economically relevant traits, enhancing breeding programs through genomic selection as well as supporting genetic studies in farmed populations Nile tilapia using dense genome-wide information.

genomics↗

bioRxiv2019

Comparative genomic analysis of three salmonid species identifies functional candidate genes involved in resistance to the intracellular bacteria Piscirickettsia salmonis

Piscirickettsia salmonis is the etiological agent of Salmon Rickettsial Syndrome (SRS), and is responsible for considerable economic losses in salmon aquaculture. The bacteria affect coho salmon (CS) (Oncorhynchus kisutch), Atlantic salmon (AS) (Salmo salar) and rainbow trout (RT) (Oncorhynchus mykiss) in several countries, including: Norway, Canada, Scotland, Ireland and Chile. We used Bayesian genome-wide association (GWAS) analyses to investigate the genetic architecture of resistance to P. salmonis in farmed populations of these species. Resistance to SRS was defined as the number of days to death (DD) and as binary survival (BS). A total of 828 CS, 2,130 RT and 2,601 AS individuals were phenotyped and then genotyped using ddRAD sequencing, 57K SNP Affymetrix(R) Axiom(R) and 50K Affymetrix(R) Axiom(R) SNP panels, respectively. Both trait of SRS resistance in CS and RT, appeared to be under oligogenic control. In AS there was evidence of polygenic control of SRS resistance. To identify candidate genes associated with resistance, we applied a comparative genomics approach in which we systematically explored the complete set of genes adjacent to SNPs which explained more than 1% of the genetic variance of resistance in each salmonid species (533 genes in total). Thus, genes were classified based on the following criteria: i) shared function of their protein domains among species, ii) shared orthology among species, iii) proximity to the SNP explaining the highest proportion of the genetic variance and, iv) presence in more than one genomic region explaining more than 1% of the genetic variance within species. Our results allowed us to identify 120 candidate genes belonging to at least one of the four criteria described above. Of these, 21 of them were part of at least two of the criteria defined above and are suggested to be strong functional candidates influencing P. salmonis resistance. These genes are related to diverse biological processes, such as: kinase activity, GTP hydrolysis, helicase activity, lipid metabolism, cytoskeletal dynamics, inflammation and innate immune response, which seem essential in the host response against P. salmonis infection. These results provide fundamental knowledge on the potential functional genes underpinning resistance against P. salmonis in three salmonid species.

genomics↗

bioRxiv2019

Fine mapping using whole-genome sequencing confirms anti Mullerian hormone as a major gene for sex determination in farmed Nile tilapia (Oreochromis niloticus L.)

Nile tilapia (Oreochromis niloticus) is one of the most cultivated and economically important species in world aquaculture. Faster male development during grow-out phase is considered a major problem that generate heterogeneous sizes of fish at harvest. Identifying genomic regions associated with sex determination in Nile tilapia is a research topic of great interest. The objective of this study was to identify genomic variants associated with sex determination in three commercial populations of Nile tilapia. Whole-genome sequencing of 326 individuals was performed, and a total of 2.4 million high-quality bi-allelic single nucleotide polymorphisms (SNPs) were identified. A genome-wide association study (GWAS) was conducted to identify markers associated with the binary sexual trait (males = 0; females = 1). A mixed logistic regression GWAS model was fitted and a genome-wide significant signal comprising 36 SNPs, located on chromosome 23 spanning a genomic region of 536 kb, was identified. Ten out of these 36 genetic variants, intercept the anti-Mullerian hormone gene. Other significant SNPs were located in the neighboring Amh gene region. This gene has been strongly associated with sex determination in several vertebrate species, playing an essential role in the differentiation of male and female reproductive tissue in early stages of development. This finding provides useful information to better understand the genetic mechanisms underlying sex determination in Nile tilapia.

genomics↗

bioRxiv2018

Heart evoked brain oscillatory networks and its interruption in early stages of Alzheimer’s disease

Understanding how the heart influences brain dynamics will suppose a deep change for the neuroscience, psychology and medicine. A mainstay questions is the heart modulation of resting state brain networks and its relation with both the cardiac dynamics and the cognitive status. We evaluated the heart evoked basal networks for controls and two groups of mild cognitive impairment patients, stable and progressive to Alzheimers disease without cardiovascular alteration symptoms. Our results in controls show that a healthy cognitive performance correlates with the heart modulation of brain dynamics in areas of the default mode network, and that the heart influence on brain networks varies along the cardiac cycle and the spectral band. However, the cognitive deficit produced by dementia correlates with the lack of heart modulation on brain activity. The heart influence on brain networks is disrupted in patients by producing hypersynchronization, accompanied by decreased cardiac complexity. We designed a surrogate and predictive procedure based on machine learning to compare the heart evoked results with the neural activity no locked to heartbeats. Based on our longitudinal data, we conclude that the prediction to progression to Alzheimers disease is higher when considering the heart - brain interaction than when taking into account only the brain dynamics. We can conclude that brain networks in control subjects were more responsive to the heart cycle, allowing a wealthier, more complex pattern of oscillations. Our results highlight the role of heart in cognitive neuroscience by showing that basal brain networks are modulated by the cardiac dynamics.

neuroscience↗

bioRxiv2018

Population genomic structure and genome-wide linkage disequilibrium in farmed Atlantic salmon (Salmo salar L.) using dense SNP genotypes

Chilean Farmed Atlantic salmon (Salmo salar) populations were established with individuals of both European and North American origins. These populations are expected to be highly genetically differentiated due to evolutionary history and poor gene flow between ancestral populations from different continents. The extent and decay of linkage disequilibrium (LD) among single nucleotide polymorphism (SNP) impacts the implementation of genome-wide association studies and genomic selection and provides relevant information about demographic processes of fish populations. We assessed the population structure and characterized the extent and decay of LD in three Chilean commercial populations of Atlantic salmon with North American (NAM), Scottish (SCO) and Norwegian (NOR) origin. A total of 151 animals were genotyped using a 159K SNP Axiom(R) myDesign Genotyping Array. A total of 40K, 113K and 136 K SNP markers were used for NAM, SCO and NOR populations, respectively. The principal component analysis explained 86.7% of the genetic diversity between populations, clearly discriminating between populations of North American and European origin, and also between European populations. Admixture analysis showed that the Scottish and North American populations likely come from one ancestral population, while the Norwegian population probably originated from more than one. NAM had the lowest effective size, followed by SCO and NOR. Large differences in the LD decay were observed between populations of North American and European origin. A r2 threshold of 0.2 was estimated for marker pairs separated by 8,000 Kb, 42 and 64 Kb in the NAM, NOR and SCO populations, respectively. In this study we show that this SNP panel can be used to detect association between markers and traits of interests and also to capture high-resolution information for genome-enabled predictions. Also, we suggest the feasibility to achieve higher prediction accuracies by using a small SNP data set as was used with the NAM population.

genomics↗