Biology subjects

Hansen, M. E.

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

6 recordsLinked to original sources

bioRxiv2025

Different artificial light modalities during daytime have all positive effects on attention and alertness

Light exposure during the day exerts acute effects on attention, such as how alert and ready a person is for solving problems and goal-oriented behavior. However, to increase the understanding of how different light conditions during daytime affect our attention, there is a need for more studies. The current study, using a sample of healthy, young adults (N = 39; 21.7{+/-}2.6 y, 61.5% female), tested the acute effects of morning exposure (09:00-11:00) to four artificial lights on attention and alertness with the Psychomotor Vigilance Task (PVT). The PVT was administered three times in short-wavelength "blue" light [SWL, high melanopic illuminance], long-wavelength "red" light [LWL, low melanopic illuminance], and bright white light [BWL] of high correlated color temperature, and white dim light [DL] as control condition. PVT measures included fluctuations in attention, quantified as intra-individual Reaction Time (RT) variability and the number of lapses; mean RT; and optimum response capability (10% fastest RTs). Compared to DL, participants had significantly fewer lapses and faster mean RT during SWL and LWL, and they enhanced their optimum responses in LWL. There were no significant effects of BWL, and light did not affect RT variability. Surprisingly, SWL was not superior to LWL. Hence, our results suggest that light of both high and low melanopic illuminance can improve alertness and attention in the morning.

neuroscience↗

bioRxiv2021

Contiguously-hydrophobic sequences are functionally significant throughout the human exome

Hydrophobic interactions have long been established as essential to stabilizing structured proteins as well as drivers of aggregation, but the impact of hydrophobicity on the functional significance of sequence variants has rarely been considered in a genome-wide context. Here we test the role of hydrophobicity on functional impact using a set of 70,000 disease and non-disease associated single nucleotide polymorphisms (SNPs), using enrichment of disease-association as an indicator of functionality. We find that functional impact is uncorrelated with hydrophobicity of the SNP itself, and only weakly correlated with the average local hydrophobicity, but is strongly correlated with both the size and minimum hydrophobicity of the contiguous hydrophobic domain that contains the SNP. Disease-association is found to vary by more than 6-fold as a function of contiguous hydrophobicity parameters, suggesting utility as a prior for identifying causal variation. We further find signatures of differential selective constraint on domain hydrophobicity, and that SNPs splitting a long hydrophobic region or joining two short regions of contiguous hydrophobicity are particularly likely to be disease-associated. Trends are preserved for both aggregating and non-aggregating proteins, indicating that the role of contiguous hydrophobicity extends well beyond aggregation risk. Statement of SignificanceProteins rely on the hydrophobic effect to maintain structure and interactions with the environment. Surprisingly, no signs that amino acid hydrophobicity influences natural selection have been detected using modern genetic data. This may be because analyses that treat each amino acid separately do not reveal significant results, which we confirm here. However, because the hydrophobic effect becomes more powerful as more hydrophobic molecules are introduced, we tested whether unbroken stretches of hydrophobic amino acids are under selection. Using genetic variant data from across the human genome, we found evidence that selection pressure increases continually with the length of the unbroken hydrophobic sequence. These results could lead to improvements in a wide range of genomic tools as well as insights into disease and protein evolutionary history.

genomics↗

bioRxiv2020

ZZ Top: faster and more adaptive Z chromosome evolution in two Lepidoptera

The rate of divergence for Z or X chromosomes is theoretically predicted to be greater than autosomes, but the possible explanations for this pattern vary, as do empirical results from diverse taxa. Even among moths and butterflies (Lepidoptera), which generally share a single-origin Z chromosome, the handful of available studies give mixed support for faster or more adaptive evolution of the Z chromosome, depending on the species assayed. Here, we examine the molecular evolution of Z chromosomes in two additional lepidopteran species: the Carolina sphinx moth and the monarch butterfly, the latter of which possesses a recent chromosomal fusion yielding a segment of newly Z-linked DNA. We find evidence for both faster and more adaptive Z chromosome evolution in both species, though this effect is strongest in the neo-Z portion of the monarch sex chromosome. The neo-Z is less male-biased than expected of a Z chromosome, and unbiased and female-biased genes drive the signal for adaptive evolution here. Together these results suggest that male-biased gene accumulation and haploid selection have opposing effects on long-term rates of adaptation and may help explain the discrepancies in previous findings as well as the repeated evolution of neo-sex chromosomes in Lepidoptera.

evolutionary biology↗

bioRxiv2019

Nanotopography enhances dynamic remodeling of tight junction proteins through cytosolic complexes

The epithelial tight junction regulates barrier function and is responsive to extracellular stimuli. Here we demonstrated that contact of synthetic surfaces with defined nanotopography at the apical surface of epithelial monolayers increased paracellular permeability of macromolecules. To monitor changes in tight junction morphology in live cells, we fluorescently tagged the scaffold protein zonula occludens-1 (ZO-1) through CRISPR/Cas9-based gene editing. Contact between cells and nanostructured surfaces destabilized junction-associated ZO-1 and promoted its arrangement into highly dynamic non-junctional cytosolic complexes that averaged [~]2 m in diameter. Junction-associated ZO-1 rapidly remodeled, and we also observed the direct transformation of cytosolic complexes into junction-like structures. Claudin-family tight junction transmembrane proteins and F-actin also were associated with these ZO-1 containing cytosolic complexes. These data suggest that the cytosolic structures are novel intermediates formed in response to nanotopographic cues that facilitate rapid tight junction remodeling in order to regulate paracellular permeability.

cell biology↗

bioRxiv2019

Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass-indexes

Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely under-represented in genomic studies. Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of Body Mass Index (BMI) in three population-based cohorts from Northeast (Salvador), Southeast (Bambui) and South (Pelotas) of the country. We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p= 2.76 e-06). This variant is very rare in Europeans but with frequencies of ~3% in West Africa, and has a strong female-specific effect (95%CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat-mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from Sao Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among morbidly obese women from Pelotas, Sao Paulo, and Bambui. The effect size of rs114066381 is at least five-times the effect size of the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects, and for which we replicated associations in Pelotas. We demonstrate how, after a decade of GWAS mostly performed in European-ancestry populations, non-European and admixed populations are a source of new relevant phenotype-associated genetic variants.

genetics↗

bioRxiv2018

Adaptive evolution of sperm proteins depends on sperm competition in a pair of Lepidoptera

Recent theory posits that adaptive evolution of reproductive proteins should depend on rates of female remating. In particular, selection on reproductive proteins is proposed to be weak unless females remate frequently, in which case cryptic female choice and sperm competition impose stronger selection. Here, we test these predictions by explicitly examining the role of selection in the molecular evolution of sperm genes in Lepidoptera, the butterflies and moths. Males of this order produce both fertilizing eupyrene sperm and a secondary apyrene type that lacks DNA. Based on population genetic analyses in two species, the monandrous Carolina sphinx moth and the highly polyandrous monarch butterfly, we see evidence for increased selection in fertilizing sperm, but only in the polyandrous species. This signal comes primarily from a decrease in non-synonymous polymorphism in sperm proteins compared to the rest of the genome, indicative of strong purifying selection. Investigation of the distribution of fitness effects of new non-synonymous mutations in monarch sperm confirms stronger selection on sperm proteins in monarchs, with very few neutral variants and weakly deleterious variants and a preponderance of strongly deleterious variants. Additionally, sperm genes in the monarch show an elevation of beneficial variants compared to the rest of the genome, suggesting a role for increased positive selection. Our results suggest that sperm competition can be a powerful selective force at the sequence level as well.

evolutionary biology↗