Biology subjects

Lucero, E.

Publications and source records attributed to Lucero, E..

3 recordsLinked to original sources

bioRxiv2026

Region-specific patterns of sexual shape variation in the human bony labyrinth: 3D geometric morphometric analysis of a sample with known genomic sex

The human bony labyrinth has attracted increasing interest because of its taxonomic, evolutionary, and functional significance. Although sexual dimorphism has been reported in several aspects of the temporal bone, the extent to which sex, age, size, and allometry contribute to labyrinth shape variation remains poorly understood. Here, we investigated patterns of sexual shape variation in the human bony labyrinth using three-dimensional geometric morphometrics in a sample of 98 archaeological individuals from South America with known genomic sex. Centroid size and allometric effects were assessed in a subset of 90 individuals with comparable metric scaling. In addition to analysing the complete labyrinth, the cochlea and semicircular canals were examined separately to evaluate region-specific patterns of sexual shape variation. Principal Component Analysis showed extensive overlap between females and males, and overall labyrinth shape did not differ significantly between sexes. Males exhibited significantly larger labyrinths than females, and centroid size explained a small but significant proportion of overall shape variation. Regional analyses showed no evidence of significant sexual shape differences in the cochlea or in any individual semicircular canal when analysed separately. In contrast, the combined semicircular canal system exhibited subtle but significant sexual shape variation independent of centroid size, whereas morphological disparity did not differ between sexes. The geometric comparison of the female and male consensus configurations further showed that sexual shape variation was regionally heterogeneous. Whereas the cochlea exhibited a pattern of localized changes with low directional coherence, the semicircular canals displayed more coordinated regional shape changes. The male consensus also exhibited slightly higher canal circularity across all three semicircular canals, particularly the posterior canal, while differences in canal-plane orientation remained minimal. These findings demonstrate that sexual shape variation in the human bony labyrinth is subtle and anatomically partitioned among its components. Although significant sex differences in centroid size were detected across most anatomical regions, overall labyrinth shape and cochlear morphology were primarily influenced by allometry, whereas significant sex-related shape differences were detected only when the semicircular canals were considered as an integrated anatomical system. These findings demonstrate that sexual dimorphism in the human bony labyrinth is subtle but regionally heterogeneous, with the cochlea and semicircular canals exhibiting distinct patterns of shape variation, suggesting that these structures are influenced by different developmental, functional, and evolutionary processes.

evolutionary biology↗

bioRxiv2025

Adrenergic Hypersensitivity Drives Ventricular Arrhythmias Following Loss of Plexin-Mediated Cardiac Innervation

BackgroundVentricular arrhythmias (VAs) are a leading cause of death and arise from a combination of cardiac muscle injury and dysfunction of the intramyocardial sympathetic nerves that control cardiac electrophysiology. The adrenergic mechanisms by which intramyocardial nerves contribute to arrhythmogenesis are poorly understood. Semaphorin-plexin signaling pathways are responsible for developmental guidance of sympathetic nerves onto the heart and have previously been associated with VAs in humans. ObjectiveTo investigate adrenergic control of arrhythmogenesis, we probed the cardiac electrophysiology of a Plexin-A3/-A4 double knockout mouse with loss of cardiac adrenergic nerves. MethodsWe studied cardiac structure and function using tissue clearing, immunohistochemistry, and echocardiography. We utilized ECG and optical mapping of action potentials to evaluate electrophysiologic responses to pharmacologic beta ({beta})-adrenergic stimulation and blockade. We measured circulating catecholamines and quantified {beta}-adrenergic receptor ({beta}AR) density in cardiac membranes. Finally, we performed a phenome-wide association study utilizing data from the UK Biobank to search for associations between PLXNA4 and human arrhythmias. ResultsMice with loss of plexin-dependent cardiac innervation had structurally normal hearts but displayed spontaneous VAs driven by adrenergic hypersensitivity, as well as increased cardiac {beta}AR density. Several human PLXNA4 variants were associated with arrhythmia phenotypes. ConclusionThese data establish a model of VAs driven by enhanced adrenergic receptor signaling, in the absence of structural heart disease, which can be used to investigate adrenergic mechanisms of arrhythmogenesis and to identify novel antiarrhythmic targets.

physiology↗

bioRxiv2021

Imipramine and olanzapine block apoE4-catalyzed polymerization of Aβ and show evidence of improving Alzheimer's disease cognition

The apolipoprotein E (APOE) {varepsilon}4 allele confers the strongest risk for late-onset Alzheimers disease (AD) besides age itself, but the mechanism(s) underlying this risk are debated. The critical test of any proposed AD mechanism is whether it leads to effective treatments. We developed a high-throughput assay to identify inhibitors of apoE4-catalyzed polymerization of the amyloid {beta} (A{beta}) peptide into neurotoxic fibrils. Screening a human drug library, we identified five non-toxic, blood-brain-barrier-permeable hit compounds that reduced apoE4-promoted A{beta} and tau neuropathology in cultured neurons. Two hit compounds, imipramine and olanzapine, but not other (non-hit) antipsychotics or antidepressants, when prescribed to AD patients for their normal clinical indications, led to improvements in cognition and clinical diagnosis. Imipramine and olanzapine have no structural, functional, or clinical similarities other than their ability to inhibit apoE4-catalyzed A{beta} polymerization, thus identifying this mechanism as an essential contribution of apoE4 to AD. One Sentence SummaryHigh-throughput drug screens, studies in Alzheimers disease cell culture models, and analyses of human clinical data identified inhibitors of the apoE4-A{beta} interaction as a novel class of Alzheimers disease therapeutics.

neuroscience↗