Biology subjects

Hernandez, C. E.

Publications and source records attributed to Hernandez, C. E..

7 recordsLinked to original sources

bioRxiv2026

Microbial Diversity and Differentiating Factors of Cocoa Fermentation Systems: Nutritional Supplementation as a Modulation Strategy Assessed by Metabarcoding

Cocoa fermentation is a spontaneous microbe-driven process in which yeasts, lactic acid bacteria (LAB), and acetic acid bacteria (AAB) generate the flavor precursors that determine the sensory quality of chocolate. Although the microbial ecology of cocoa fermentation has been increasingly studied through culture-independent methods, the effect of targeted nutritional interventions on community structure within geographically defined production territories has received limited attention. Here, we employed dual-marker metabarcoding (16S rRNA V4 and ITS1) with Illumina NovaSeq 6000 sequencing to characterize bacterial and fungal communities during spontaneous fermentation of Trinitario cocoa beans subjected to amino acid and zinc supplementation in the Limon province of Costa Rica. Fifteen samples were collected at 0, 24, and 48 h from control, amino acid-supplemented, and zinc-supplemented fermentations, each in duplicate. The bacterial community comprised 292 amplicon sequence variants (ASVs) representing 88 genera across 15 phyla; the fungal community comprised 1,117 ASVs representing 248 genera across 9 phyla. Firmicutes and Proteobacteria dominated the bacterial fraction, with a pronounced shift from Tatumella-dominated fresh pulp toward Weissella- and Leuconostoc-rich assemblages during fermentation. Amino acid supplementation reduced Firmicutes at 48 h while favoring Acetobacter proliferation; zinc supplementation promoted Mucoromycota and Wickerhamomyces while sustaining Liquorilactobacillus abundance. Beta diversity analyses (Aitchison distance, weighted and unweighted UniFrac) confirmed significant compositional differences between treatments (PERMANOVA, p [≤] 0.01), although alpha diversity indices did not differ between individual treatment pairs. Sparse Estimation of Correlations among Microbiomes (SECOM) revealed structured co-occurrence networks, including positive associations between Gluconobacter and Acetobacter and negative associations between Tatumella and several AAB genera. Predicted functional profiles (PICRUSt2) showed no significant pathway-level differences. Taken together, these results show that nutritional supplementation can reshape microbial community composition without reducing overall diversity. This provides a viable approach for steering fermentation outcomes in cocoa-producing territories that seek quality differentiation.

microbiology↗

bioRxiv2026

Genomic sampling and population structure of farmer-maintained varieties reveal previously uncharacterized diversity of Theobroma cacao L. in Costa Rica

Understanding crop genetic diversity is essential for conservation and breeding, yet farmer-maintained germplasm remains largely underrepresented in genomic studies. Theobroma cacao L. has a complex domestication history and extensive global diversity, and cacao currently cultivated in Central America, particularly in Costa Rica, has been understudied compared to South American and Mexican cultivars despite cultural and historical importance. In this study, we investigate the genetic diversity of cacao from farmer-managed systems across Costa Rica to search for Criollo germplasm and identify and characterize any unique local genetic groups. Ninety-four trees were sampled from 17 farms across four regions of the country and sequenced using whole genome resequencing. Farmer materials were analyzed alongside 166 previously characterized reference accessions representing major cacao genetic groups. Population structure analyses, phylogenetic reconstruction, and network approaches revealed that Costa Rican cacao encompasses multiple known genetic groups, including Criollo-derived lineages, while also harboring locally distinct diversity not fully represented in current global reference collections. Analyses revealed close kinship between many accessions with no clear geographic patterns corresponding to the observed population differentiation, reflecting the effects of farmers in creating dominant patterns of gene flow through seed-saving, clonal propagation, and sharing genotypes among farms. Heterozygosity levels varied substantially among individuals, consistent with a mixture of highly inbred Criollo trees and more heterozygous, admixed genotypes. We find that farmer-managed cacao systems are reservoirs of genetic diversity, including possibly rare or historically important lineages, underscoring the value of these farming systems for effective conservation and management of genomic resources for cacao resilience and improvement.

genomics↗

bioRxiv2025

Fusobacteria nucleatum determines the expression of amphetamine-induced behavioral responses through an epigenetic phenomenon.

Amphetamines (AMPHs) are psychostimulants commonly used for the treatment of neuropsychiatric disorders. They are also misused (AMPH use disorder; AUD), with devastating outcomes. Recent studies have implicated dysbiosis in the pathogenesis of AUD. However, the mechanistic roles of microbes in AUD are unknown. Fusobacterium nucleatum (Fn) is a bacterium that increases in abundance in both rats and humans upon AMPH exposure. Fn releases short-chain fatty acids (SCFAs), bacterial byproducts thought to play a fundamental role in the gut-brain axis as well as the pathogenesis of AUD. We demonstrate that in gnotobiotic Drosophila melanogaster, colonization with Fn or dietary supplementation of the SCFA butyrate, a potent inhibitor of histone deacetylases (HDACs), enhances the psychomotor and rewarding properties of AMPH as well as its ability to promote male sexual motivation. Furthermore, solely HDAC1 RNAi targeted inhibition recapitulates these enhancements, pointing to a specific process underlying this Fn phenomenon. Of note is that the expression of these AMPH behaviors is determined by the increase in extracellular dopamine (DA) levels that result from AMPH-induced reversal of DA transporter (DAT) function, termed non-vesicular DA release (NVDR). The magnitude of AMPH-induced NVDR is dictated, at least in part, by DAT expression levels. Consistent with our behavioral data, we show that Fn, butyrate, and HDAC1 inhibition enhance NVDR by elevating DAT expression. Thus, the participation of Fn in AUD stems from its ability to release butyrate and inhibit HDAC1. These data offer a microbial target and probiotic interventions for AUD treatment.

neuroscience↗

bioRxiv2021

DARPP-32 promotes ERBB3-mediated resistance to molecular targeted therapy in EGFR-mutated lung adenocarcinoma

While molecular targeted therapies have improved prognoses of advanced stage lung adenocarcinoma expressing oncogenic driver mutations, acquired therapeutic resistance continues to be a major problem. Epidermal growth factor receptor (EGFR) activating mutations are among the most common targetable genetic alterations in lung adenocarcinoma, and EGFR tyrosine kinase inhibitors (TKIs) are recommended first-line therapy for EGFR mutation positive cancer patients. Unfortunately, most patients develop resistance to EGFR TKIs and rapid disease progression occurs. A better mechanistic understanding of therapy refractory cancer progression is necessary to develop new therapeutic approaches to predict and prevent acquired resistance to EGFR TKIs. Here, we identify a new mechanism of ERBB3-mediated resistance to EGFR TKIs in human lung adenocarcinoma. Specifically, we show that dopamine and cyclic AMP-regulated phosphoprotein, Mr 32000 (DARPP-32) physically recruits ERBB3 to EGFR to mediate a switch from EGFR homodimers to EGFR:ERBB3 heterodimers to bypass EGFR TKI-mediated inhibition to potentiate ERBB3-dependent activation of oncogenic AKT and ERK signaling that drives therapy refractory tumor cell survival. In a cohort of paired tumor specimens derived from 30 lung adenocarcinoma patients before and after the development of EGFR TKI refractory disease progression, we reveal that DARPP-32 as well as kinase-activated EGFR and ERBB3 proteins are overexpressed upon acquired EGFR TKI resistance. In vivo studies suggest that ablation of DARPP-32 protein activity sensitizes gefitinib-resistant lung tumor xenografts to EGFR TKI treatment, while DARPP-32 overexpression increases gefitinib-refractory lung cancer progression in gefitinib-sensitive lung tumors orthotopically xenografted into mice. Taken together, our findings introduce a DARPP-32-mediated, ERBB3-dependent mechanism used by lung tumor cells to evade EGFR TKI-induced cell death, potentially paving the way for the development of new therapies to prevent or overcome therapy-refractory lung adenocarcinoma progression.

cancer biology↗

bioRxiv2020

Shrinking of fish under warmer temperatures decrease dispersal abilities and speciation rates

There is an ongoing debate as to whether fish body size will decrease with global warming and how body size changes may impact dispersal abilities and speciation rates. Although theory predicts that, when fish face warmer temperatures, they grow to smaller adult sizes, see a reduction in their ability to move, and increase their probability of speciation, evaluations of such predictions are hampered owing to the lack of empirical data spanning both wide temporal and geographical scales. Here, using phylogenetic methods, temperature, and 21,895 occurrences for 158 worldwide-distributed species of fish, we show that smaller fish have occurred in warmer waters for over 150 million years and across marine and freshwater realms. Smaller fish have historically moved the shortest distances and at low speeds. In addition, small fish display the lowest probability of giving rise to new species. Further, we found that species of fish that displayed high speeds of geographical movement and rates of size evolution experienced higher rates of temperature change in their lineage. Taking these results together, global warming predicts a future where smaller fish that have reduced ability to move over aquatic systems will be more prevalent, in turn, this will result in fewer species contributing global biodiversity.

evolutionary biology↗

bioRxiv2019

Global drivers of diversification in a marine species complex

Investigating historical gene flow in species complexes can indicate how environmental and reproductive barriers shape genome divergence before speciation. The processes influencing species diversification under environmental change remain one of the central focal points of evolutionary biology, particularly for marine organisms with high dispersal potential. We investigated genome-wide divergence, introgression patterns and inferred demographic history between species pairs of all extant rock lobster species (Jasus spp.), a complex with long larval duration, that has populated continental shelf and seamount habitats around the globe at approximately 40{degrees}S. Genetic differentiation patterns revealed the effects of the environment and geographic isolation. Species associated with the same habitat structure (either continental shelf or seamount/island) shared a common ancestry, even though the habitats were not adjacent. Differences in benthic temperature explained a significant proportion (41.3%) of the genetic differentiation. The Eastern Pacific species pair of J. caveorum and J. frontalis retained a signal of strict isolation following ancient migration, whereas species pairs from Australia and Africa and seamounts in the Indian and Atlantic oceans included events of introgression after secondary contact. Parameters estimated for time in isolation and gene flow were congruent with genetic differentiation metrics suggesting that the observed differentiation patterns are the product of migration and genetic drift. Our results reveal important effects of habitat and demographic processes on the divergence of species within the genus Jasus providing the first empirical study of genome-wide drivers of diversification that incorporates all extant species in a marine genus with long pelagic larval duration.

evolutionary biology↗

bioRxiv2019

ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumor cell survival

Small cell lung cancer (SCLC) is the most aggressive form of lung cancer, and new molecular insights are necessary for prognostic and therapeutic advances. Here we demonstrate in orthotopic mouse models that dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) and its N-terminally truncated splice variant t-DARPP promote SCLC growth through increased proliferation, Akt/Erk-mediated survival and anti-apoptotic signaling. DARPP-32 and t-DARPP proteins are overexpressed in SCLC patient-derived tumor tissue, but virtually undetectable in physiologically normal lung. RNA sequencing analysis reveals a subset of SCLC patients with high tumoral t-DARPP expression and upregulated Notch signaling genes, including achaete-scute homologue 1 (ASCL1). We show that DARPP-32 isoforms are transcriptionally activated by ASCL1 in human SCLC cells. Taken together, we demonstrate new regulatory mechanisms of SCLC oncogenesis that suggest DARPP-32 isoforms may represent a negative prognostic indicator for SCLC and serve as a potential target for the development of new therapies.

cancer biology↗