Biology subjects

Herrera, J.

Publications and source records attributed to Herrera, J..

9 recordsLinked to original sources

bioRxiv2025

Amazon biodiversity is at risk from metal contamination due to mining activity

The Amazon basin hosts the most biodiverse and intact ecosystems on Earth, yet human activities are an increasing threat. Metal contamination due to mining constitutes one of these major threats, but its impacts remain poorly quantified. We provide the first quantitative assessment of biodiversity exposure to mining-associated metals--mercury [Hg], arsenic [As], copper [Cu], Zinc [Zn], and lead [Pb]--across the Amazon. Around 66% of the Amazons 38,890 species of birds, plants, mammals, reptiles, amphibians, and fishes are exposed to metal contamination, including biodiversity hotspots and Indigenous territories. Safeguarding the Amazons role as a global reservoir of biodiversity, ecosystem function, and cultural heritage requires addressing metal contamination not only as a localized issue, but as a pervasive threat to global biodiversity.

ecology↗

bioRxiv2025

Epigenetic and Transcriptomic Alterations Precede Amyloidosis in the Hippocampus of the Alzheimer's Disease AppNL-G-F Knock in Mouse Model

Detecting and understanding the early stages of Alzheimers disease (AD) is essential for uncovering initial mechanisms of neuropathology and devising effective interventions. In this study, we leveraged the humanized AppNL-G-F mouse which exhibits early-onset amyloid pathology with a predictable timeline, to investigate molecular changes in the hippocampus and blood before the onset of severe neuropathology and independent of aging. Employing a multi-omics approach, we identified alterations in chromatin accessibility, gene expression, and DNA methylation associated with early amyloidosis. Chromatin accessibility changes were prominent in excitatory neurons during early pathology, with a later shift to inhibitory neurons, potentially reflecting compensatory mechanisms to mitigate excitatory neuron dysregulation. Despite broadly comparable hippocampal cell composition, transcriptomic comparisons between wild-type and AppNL-G-F mice revealed major gene expression differences, particularly in pathways related to mitochondrial function and protein biosynthesis, preceding severe amyloid plaque deposition. In later stages, upregulation of immune and neuroinflammatory pathways was observed, aligning with established neuroinflammatory processes in AD. Additionally, we identified extensive DNA methylation differences in both the blood and hippocampus of AppNL-G-Fmice during early and late stages of pathology. Many differentially methylated regions in the blood, even at early pathology stages, were associated with cis-regulatory elements in the brain and were located near differentially expressed genes in the hippocampus. These regions were enriched in pathways associated with brain function, including neuron development and synaptic processes, highlighting a connection between blood methylation patterns and brain activity. This finding suggests the potential use of blood DNA methylation as a biomarker for the early detection of amyloidosis. Notably, we identified five candidate biomarker genes, including Rbfox1 and Camta1, with epigenetic dysregulation detectable in both the brain and blood prior to severe amyloid accumulation. Our study, leveraging a unique AD mouse model and a multi-omics approach, highlights epigenetic signatures of AD before the onset of clinical symptoms, providing a foundation for future research into early diagnosis and therapeutic strategies, as well as potential blood biomarkers.

molecular biology↗

bioRxiv2025

Quiescence modulates age-related changes in the functional capacity of highly proliferative canine lung mesenchymal stromal cell populations

The functional capacity of highly proliferative cell populations changes with age. Here, we report that the proliferative capacity of canine lung mesenchymal stromal cells (LMSCs) declines with increasing age of the donor. However, other functional changes such as reduced autophagy, reduced migration/wound healing, increased production of reactive oxygen species, and increased senescence are not significantly altered with increasing age. Furthermore, transcriptomic profiling suggests minimal age-related changes. These data suggest that the reduced proliferative capacity of lung LMSCs isolated from aging donors may be associated with reversible cell cycle arrest (quiescence), rather than irreversible cell cycle arrest (senescence). Similar findings have been reported in other systems, including neural and muscle stem cells that are associated with low turnover-rate tissues.

developmental biology↗

bioRxiv2025

Non-mutated human tau stimulates Alzheimer's disease-relevant neurodegeneration in a microglia-dependent manner

The accumulation of abnormal, non-mutated tau protein is a key pathological hallmark of Alzheimers disease (AD). Despite its strong association with disease progression, the mechanisms by which tau drives neurodegeneration in the brain remain poorly understood. Here, we selectively expressed non-mutated or mutated human microtubule-associated protein tau (hMAPT) in neurons across the brain and observed neurodegeneration in the hippocampus, especially associated with non-mutated human tau. Single-nuclei RNA sequencing confirmed a selective loss of hippocampal excitatory neurons by the wild-type tau and revealed the upregulation of neurodegeneration-related pathways in the affected populations. The accumulation of phosphorylated tau was accompanied by cellular stress in neurons and reactive gliosis in multiple brain regions. Notably, the lifelong absence of microglia significantly and differentially influenced the extent of neurodegeneration in the hippocampus and thalamus. Therefore, our study established an AD-relevant tauopathy mouse model, elucidated both neuron-intrinsic and neuron-extrinsic responses, and highlighted critical and complex roles of microglia in modulating tau-driven neurodegeneration.

neuroscience↗

bioRxiv2024

Deletion of an evolutionarily conserved TAD boundary compromises spermatogenesis in mice

Spermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potentially leading to male infertility. Recent research has rapidly increased the number of protein coding mutations causally linked to impaired spermatogenesis in humans and mice. However, the role of non-coding mutations remains largely unexplored. As a case study to evaluate the effects of non-coding mutations on spermatogenesis, we first identified an evolutionarily conserved topologically associated domain (TAD) boundary near two genes with important roles in mammalian testis function: Dmrtb1 and Lrp8. We then used CRISPR-Cas9 to generate a mouse line where 26kb of the boundary was removed including a strong and evolutionarily conserved CTCF binding site. ChIP-seq and Hi-C experiments confirmed the removal of the CTCF site and a resulting increase in the DNA-DNA interactions across the domain boundary. Mutant mice displayed significant changes in testis gene expression, abnormal testis histology, a 35% drop in the estimated efficiency of spermatogenesis and a 28% decrease in daily sperm production compared to littermate controls. Despite these quantitative changes in testis function, mutant mice show no significant changes in fertility. This suggests that non-coding deletions affecting testis gene regulation may have smaller effects on fertility compared to coding mutations of the same genes. Our results demonstrate that disruption of a TAD boundary can have a negative impact on sperm production and highlight the importance of considering non-coding mutations in the analysis of patients with male infertility.

genetics↗

bioRxiv2024

Phenotypic analysis of the edible fruits of Lardizabala biternata, an endemic and monotypic vine from the Chilean biodiversity hotspot in South America.

IntroductionLardizabala biternata is a vine endemic to Chile, distributed between 32{degrees}S and 40{degrees}S. Its sweet edible fruits have historically been harvested by hand from the wild as there are no productive systems for this vine. Herein, we conducted the first phenotypic analysis of L. biternata fruits, which includes qualitative and quantitative analyses of morphological and morphometric traits. This phenotypic analysis is the baseline for the development of production systems that could reduce anthropogenic pressure on wild populations and favour the ex-situ conservation of this vine. Materials and methodsWe collected 282 fruits from two geographically distant populations during four fruiting seasons. In all of them we recorded 14 morphological attributes, including total weight, length, width, height, diameter, volume, edible pulp content, seed number weight and individual seed weight. We investigated morphometric differences between populations and seasons by analysis of variance (ANOVAs), phenotypic correlations by regressions and associations between traits by principal component analysis (PCA). ResultsOn overage, fruits weighed 20.8 g (3.0 - 44.6 g) and measured 54 mm in length (20.1 - 83.4 mm) and 23.7 mm in diameter. Edible pulp contributed around 44.4% of total fruit weight. Observed traits displayed significant variations between seasons and among traits (length vs width vs height). Fruit weight showed a high correlation with edible pulp weight, fruit length, seed weight, seed number, and others. Discussion and conclusionsOur study represents the first phenotypic analysis of the fruits of this wild, endemic, and rare plant. We comprehensively describe the morphological and morphometric characteristics of its fruits. The characteristics of L. biternata fruits show significant morphometric variation between populations and seasons. However, the edible pulp consistently remains the main component of the fresh fruit weight. Like other domesticated members of the Lardizabalaceae, the fruits of this wild plant have the potential for cultivation through the development of sustainable production systems. The information we provide serves as a baseline for the development of such systems through selection and genetic improvement of the plant.

plant biology↗

bioRxiv2023

Effect of habitat degradation on hantavirus infection among introduced and endemic small mammals of Madagascar

Hantaviruses are globally distributed zoonotic pathogens capable of causing fatal disease in humans. Rodents and other small mammals are the typical reservoirs of hantaviruses, though the particular host varies regionally. Addressing the risk of hantavirus spillover from animal reservoirs to humans requires identifying the local mammal reservoirs and the predictors of infection in those animals, such as their population density and habitat characteristics. We screened native and non-native small mammals and bats in northeastern Madagascar for hantavirus infection to investigate the influence of habitat, including effects of human land use on viral prevalence. We trapped 227 bats and 1663 small mammals over 5 successive years in and around Marojejy National Park across a range of habitat types including villages, agricultural fields, regrowth areas, and secondary and semi-intact forests. Animals sampled included endemic tenrecs (Tenrecidae), rodents (Nesomyidae) and bats (6 families), along with non-native rodents (Muridae) and shrews (Soricidae). A hantavirus closely related to the previously described Anjozorobe virus infected 9.5% of Rattus rattus sampled. We did not detect hantaviruses in any other species. Habitat degradation had a complex impact on hantavirus prevalence in our study system: more intensive land use increase the abundance of R. rattus. The average body size of individuals varied between agricultural and non-agricultural land-use types, which in turn affected infection prevalence. Smaller R.rattus had lower probability of infection and were captured more commonly in villages and forests. Thus, infection prevalence was highest in agricultural areas. These findings provide new insights to the gradients of hantavirus exposure risk for humans in areas undergoing rapid land use transformations associated with agricultural practices.

zoology↗

bioRxiv2023

TAD Evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function

Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species, and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find that only 14% of all human TAD boundaries are shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons, compared to species-specific boundaries. CRISPR-Cas9 knockouts of two ultraconserved boundaries in mouse models leads to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-related AUTS2 gene results in upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations, and showcase the functional importance of TAD evolution.

evolutionary biology↗

bioRxiv2023

Circadian clock genes Bmal1 and Per2 in the nucleus accumbens are negative regulators of alcohol-drinking behavior in mice.

Voluntary alcohol consumption is influenced by a variety of environmental and genetic factors, including circadian clock genes. Even though their sex-specific role in alcohol drinking was identified through selective ablation of Bmal1 and Per2 from neurons of the mouse striatum, the contribution of specific striatal subregions to the observed drinking behavior remains unclear. Thus, alcohol intake and preference was investigated in male and female mice with a conditional knockout of Bmal1 and Per2 from cells in the nucleus accumbens (Nac). Mood- and anxiety-related behaviors were assessed prior to alcohol drinking to exclude potential confounding effects of the animals behavioral state on alcohol consumption. Alcohol consumption and preference were increased in male and female mice with a conditional knockout of Bmal1, whereas the same effect was only found in males with a deletion of Per2. Because affective behaviors were only mildly influenced by the conditional gene knockouts, observed alcohol-drinking phenotypes can be directly associated with the Nac-specific clock gene deletion. The results thus suggest an inhibitory role of Bmal1 and Per2 in the Nac on alcohol consumption in male mice. In females, the inhibitory effect of Bmal1 is strictly localized to the Nac, because striatal-wide deletion of Bmal1 caused a suppression of alcohol consumption. This sex-dependent stimulatory effect of Bmal1 on alcohol drinking is probably mediated through other striatal subregions such as the dorsal striatum.

neuroscience↗