Biology subjects

Pena, C.

Publications and source records attributed to Pena, C..

9 recordsLinked to original sources

bioRxiv2026

A prospective multi-cohort study identifies reproducible molecular responses to musical stimulation in the human tear proteome

Music elicits complex emotional, cognitive, and physiological responses, yet the molecular mechanisms underlying these effects remain poorly understood. Tear fluid is an accessible biofluid that reflects both systemic and local physiology, providing a unique opportunity to investigate the biological effects of musical stimulation. Quantitative mass spectrometry-based proteomics was performed on paired tear samples (n = 336) collected before and after exposure to a standardized musical stimulus in two independent cohorts of healthy participants, including both music-stimulated and music-unstimulated individuals. Integrative analyses, including differential expression, functional enrichment, co-expression network, correlation, and machine-learning approaches, identified reproducible molecular responses across cohorts. Fourteen proteins, including PRTN3, LEG3, CATD, IGHG2, and ZA2G, remained significant after multiple-testing correction and showed concordant regulation in the stimulated cohorts but not in controls. Functional enrichment converged on innate immune, inflammatory, host-defense, and extracellular signaling pathways, and consensus network analysis identified reproducible immune-related modules. The 14-protein signature robustly discriminated pre- and post-stimulation samples, with no effect detected in the unstimulated control groups. These findings support tear proteomics as a promising non-invasive approach for investigating the molecular basis of auditory and emotional experiences.

molecular biology↗

bioRxiv2026

Environmental Regulation and Gene-by-Environment Interaction Influence RAP1 Activity and its Impact on Gene Expression

Gene-by-environment (GxE) interactions play a major role in shaping both phenotypic and molecular variation, with important implications for human health and disease. In this study, we used the Doxycycline (Dox) regulated, tetracycline-responsive (Tet-Off) promoter system to sequentially reduce or titrate gene expression levels of the essential yeast transcription factor Repressor Activator Protein 1 (RAP1) similar to a hypomorph allele series, across three distinct environments: Yeast Peptone Dextrose (YPD) media, YPD media with Heat Shock (HS), and Yeast Peptone Acetate (YPAC) media. We then performed RNA sequencing (RNA Seq) to assess global transcriptional responses to RAP1 reduction in these different growth environments. Our analysis first focused on the independent effects of varying RAP1 expression levels within and across environments. We then explored GxE interactions, revealing a subset of genes with significant consequences of reduced levels of RAP1 and environment-specific expression patterns. Notably, many genes exhibited opposite effects of RAP1 titration on gene expression when yeast were grown in YPAC media compared to YPD media and/or HS, suggesting environment-dependent regulatory architecture. This design reveals how cells integrate internal transcriptional and regulatory changes with external environmental cues, providing a deeper view of GxE architecture. Using Weighted Gene Co-expression Network Analysis (WGCNA), we identified co-regulated gene modules, and by combining this with transcription factor motif enrichment tests, our study identified candidate regulators driving their dynamics. Our findings demonstrate that gene regulatory networks can vary dramatically depending on the environmental context an organism experiences, which can then influence the specific phenotypes produced by a particular genetic perturbation. This illustrates the complexity of genotype-environment interactions and the importance of studying gene function in multiple environments to gain a truly comprehensive understanding of a genes sometimes numerous and diverse functions.

genomics↗

bioRxiv2023

Winning a competitive research award decreases time to degree in bioscience PhD programs, but not for everyone

Time to degree completion is an important metric of academic progress and success for doctoral students. It is also a common way for educational stakeholders to compare programs even if the content of the degree programs varies. But what types of behaviors and experiences are associated with faster times to degree? In this education article, we examine the relationship between receiving competitive research awards (e.g. grant writing) and time to degree for PhD students. We organize our analyses by student identities, specifically gender and underrepresented minority (URM) status, to examine differences in time to degree based on student demographics. Our dataset included students that graduated between academic years 2008-09 through 2018-19. We also interviewed students currently enrolled in these same programs. We find that URM women who won competitive research awards graduate faster than all other students who also won awards but also report lower levels of advisor support. We also find that URM women and all URM students tended to graduate faster compared to other groups of students who did not win awards. Students who reported feeling supported by their advisors, most of which reflected hands-on guidance through the writing process, in the interviews were more likely to apply for grants. Combined, these results highlight that writing grants and specific types of advisor support may influence faster times to degree for bioscience PhD students. This study suggests similar introspective analyses at other institutions and databases are needed.

scientific communication and education↗

bioRxiv2022

An uncommon garden experiment: microenvironment has stronger influence on phenotypic variation than epigenetic memory in the clonal Lombardy poplar

Environmental changes can trigger phenotypic variation in plants through epigenetic mechanisms, but strong genetic influences on epigenetic variation and phenotypes make it difficult to isolate and study these effects. We investigated phenotypic plasticity using the Lombardy poplar (Populus nigra cv. Italica Duroi), a globaly distributed clonal tree. We surveyed 14 functional traits related to tree growth, ecophysiological and phenological processes in poplar ramets collected along a wide geographical range in Europe and planted under common garden conditions. We investigated whether phenotypic variation was related to geography and historical bioclimatic data of the ramets sites of origin using linear mixed effect models. We found significant differences in among ramets from different geographic origins in tree height, number of stems per ramet and duration of bud flush. However, microenvironmental variation in the common garden, captured via block effects, had an even bigger impact on phenotypic variation than the environmental conditions at the sites of origin. Our results show that phenotypic variation in the ramets might be associated to the climate origin from different climates, suggesting possible epigenetic memory. However, such legacy effects might be quickly outweighed by new environmental conditions.

ecology↗

bioRxiv2021

The unresolved phylogenomic tree of butterflies and moths (Lepidoptera): assessing the potential causes and consequences

The field of molecular phylogenetics is being revolutionised with next-generation sequencing technologies making it possible to sequence large numbers of genomes for non-model organisms ushering us into the era of phylogenomics. The current challenge is no longer how to get enough data, but rather how to analyse the data and how to assess the support for the inferred phylogeny. We focus on one of the largest animal groups on the planet - butterflies and moths (order Lepidoptera). We clearly demonstrate that there are unresolved issues in the inferred phylogenetic relationships of the major lineages, despite several recent phylogenomic studies of the group. We assess the potential causes and consequences of the conflicting phylogenetic hypotheses. With a dataset consisting of 331 protein-coding genes and the alignment length over 290 000 base pairs, including 200 taxa representing 81% of lepidopteran superfamilies, we compare phylogenetic hypotheses inferred from amino acid and nucleotide alignments. The resulting two phylogenies are discordant, especially with respect to the placement of the superfamily Gelechioidea, which is likely due to compositional bias of both the nucleotide and amino acid sequences. With a series of analyses, we dissect our dataset and demonstrate that there is sufficient phylogenetic signal to resolve much of the lepidopteran tree of life. Overall, the results from the nucleotide alignment are more robust to the various perturbations of the data that we carried out. However, the lack of support for much of the backbone within Ditrysia makes the current butterfly and moth tree of life still unresolved. We conclude that taxon sampling remains an issue even in phylogenomic analyses, and recommend that poorly sampled highly diverse groups, such as Gelechioidea in Lepidoptera, should receive extra attention in the future.

evolutionary biology↗

bioRxiv2020

The latitudinal diversity gradient in brush-footed butterflies (Nymphalidae): conserved ancestral tropical niche but different continental histories.

The latitudinal diversity gradient (LDG) is arguably one of the most striking patterns in nature. The global increase in species richness toward the tropics across continents and taxonomic groups stimulated the formulation of many hypotheses to explain the underlying mechanisms of this pattern. We evaluated several of these hypotheses to explain spatial diversity patterns in the butterfly family, Nymphalidae, by assessing the contributions of speciation, extinction, and dispersal to the LDG, and also the extent to which these processes differ among regions at the same latitude. We generated a new, time-calibrated phylogeny of Nymphalidae based on 10 gene fragments and containing ca. 2,800 species ([~]45% of extant diversity). Neither speciation nor extinction rate variations consistently explain the LDG among regions because temporal diversification dynamics differ greatly across longitude. For example, we found that Neotropical nymphalid diversity results from low extinction rates, not high speciation rates, and that biotic interchanges with other regions were rare. Southeast Asia was also characterized by a low speciation rate but, unlike the Neotropics, was the main source of dispersal events through time. Our results suggest that global climate change throughout the Cenozoic, particularly during the Eocene-Oligocene transition, combined with the conserved ancestral tropical niches, played a major role in generating the modern LDG of butterflies.

ecology↗

bioRxiv2019

Comprehensive characterization of the mutational landscape in localized anal squamous cell carcinoma

PurposeAnal squamous cell carcinoma (ASCC) is a rare neoplasm. Chemo-radiotherapy is the standard of care, with no therapeutic advances achieved over the past three decades. Thus, a deeper molecular characterization of this disease is still necessary.\n\nMethodsWe analyzed 46 paraffin-embedded tumor samples from patients diagnosed with primary ASCC by exome sequencing. A bioinformatics approach focused in the identification of high impact genetic variants, which may act as drivers of oncogenesis, was performed. The relation between genetics variant and prognosis was also studied.\n\nResultsThe list of high impact genetic variants was unique for each patient. However, the pathways in which these genes are involved are well-known hallmarks of cancer, such as angiogenesis or immune pathways. Additionally, we determined that genetic variants in BRCA2, ZNF750, FAM208B, ZNF599 and ZC3H13 genes are related with poor disease-free survival in ASCC.\n\nConclusionHigh impact genetic variants in ASCC affect pathways involved in cancer development, and may play a role in the etiology of the disease. Variants in BRCA2, ZNF750, FAM208B, ZNF599 and ZC3H13 genes seem to be related with prognosis in ASCC. Sequencing of ASCC clinical samples appears an encouraging tool for the molecular portrait of this disease.

cancer biology↗

bioRxiv2018

The GTPase Nog1 couples polypeptide exit tunnel quality control with ribosomal stalk assembly

Eukaryotic ribosome precursors acquire translation competence in the cytoplasm through stepwise release of bound assembly factors, and proofreading of their functional centers. In case of the large subunit precursor (pre-60S), these essential steps include eviction of placeholders Arx1 and Mrt4 that prevent premature loading of the protein-folding machinery at the polypeptide exit tunnel (PET), and the ribosomal stalk, respectively. Here, we reveal that sequential ATPase and GTPase activities license release factors Rei1 and Yvh1 recruitment to the pre-60S in order to trigger Arx1 and Mrt4 removal. Drg1-ATPase activity extracts the C-terminal tail of Nog1 from the PET, enabling Rei1 to probe PET integrity, and then catalyze Arx1 release. Subsequently, GTPase hydrolysis stimulates Nog1 removal from the pre-60S, permitting Yvh1 to mediate Mrt4 release, and initiate ribosomal stalk assembly. Thus, Nog1 couples quality control and assembly of spatially distant functional centers during ribosome formation.

biochemistry↗

bioRxiv2017

Structure of the eukaryotic cytoplasmic pre-40S ribosomal subunit

Final maturation of eukaryotic ribosomes occurs in the cytoplasm and requires the sequential removal of associated assembly factors and processing of the immature 20S pre-RNA. Using cryo-electron microscopy (cryo-EM), we have determined the structure of a cytoplasmic pre-40S particle poised to initiate final maturation at a resolution of 3.4 [A]. The structure reveals the extent of conformational rearrangements of the 3 major and 3 minor domains of the ribosomal RNA that take place during maturation, as well as the roles of the assembly factors Enp1, Ltv1, Rio2, Tsr1, and Pno1 in the process. Altogether, we provide a structural framework for the coordination of the final maturation events that drive a pre-40S particle towards the mature form capable of engaging in translation.

molecular biology↗