Biology subjects

Mills, K. L.

Publications and source records attributed to Mills, K. L..

12 recordsLinked to original sources

bioRxiv2024

Dimensions of early life adversity are differentially associated with patterns of delayed and accelerated brain maturation

BackgroundDifferent types of early-life adversity have been associated with childrens brain structure and function. However, understanding the disparate influence of distinct adversity exposures on the developing brain remains a major challenge. MethodsThis study investigates the neural correlates of 10 robust dimensions of early-life adversity identified through exploratory factor analysis in a large community sample of youth from the Adolescent Brain Cognitive Development (ABCD) Study. Brain age models were trained, validated, and tested separately on T1-weighted (T1; N = 9524), diffusion tensor (DTI; N = 8834), and resting-state functional (rs-fMRI; N = 8233) magnetic resonance imaging (MRI) data from two time points (mean age = 10.7 years, SD = 1.2, range = 8.9-13.8 years). ResultsBayesian multilevel modelling supported distinct associations between different types of early-life adversity exposures and younger- and older-looking brains. Dimensions generally related to emotional neglect, such as lack of primary and secondary caregiver support, and lack of caregiver supervision, were associated with lower brain age gaps (BAGs), i.e., younger-looking brains. In contrast, dimensions generally related to caregiver psychopathology, trauma exposure, family aggression, substance use and separation from biological parent, and socio-economic disadvantage and neighbourhood safety were associated with higher BAGs, i.e., older-looking brains. ConclusionsThe findings suggest that dimensions of early-life adversity are differentially associated with distinct neurodevelopmental patterns, indicative of dimension-specific delayed and accelerated brain maturation.

neuroscience↗

bioRxiv2023

A highly resolved multiplex network reveals the structural role of insects and plants in terrestrial food webs

Comparative studies suggest remarkable similarities among food webs across habitats, including systematic changes in their structure with diversity and complexity (scale-dependence). However, historic aboveground terrestrial food webs (ATFWs) have coarsely grouped plants and insects such that these webs are generally small, and herbivory is disproportionately underrepresented compared to vertebrate predator-prey interactions. Furthermore, terrestrial herbivory is thought to be structured by unique processes compared to size-structured feeding in other systems. Here, we present the richest ATFW to date, including [~]580,000 feeding links among [~]3,800 taxonomic species, sourced from [~]27,000 expert-vetted interaction records annotated as feeding upon one of six different resource types: leaves, flowers, seeds, wood, prey, and carrion. By comparison to historical ATFWs and null ecological hypotheses, we show that our temperate forest web displays a potentially unique structure characterized by two properties: a) a large fraction of carnivory interactions dominated by a small number of hyper-generalist, opportunistic bird and bat predators, and b) a smaller fraction of herbivory interactions dominated by a hyper-rich community of insects with variably-sized but highly-specific diets. We attribute our findings to the large-scale, even resolution of vertebrate, insect, and plant guilds in our food web.

ecology↗

bioRxiv2023

BrainAGE as a measure of maturation during early adolescence

The Brain-Age Gap Estimation (BrainAGE) is an important new tool that purports to evaluate brain maturity when used in adolescent populations. However, it is unclear whether BrainAGE tracks with other maturational metrics in adolescence. In the current study, we related BrainAGE to metrics of pubertal and cognitive development using both a previously validated model and a novel model trained specifically on an early adolescent population. The previously validated model was used to predict BrainAGE in two age bands, 9-11 and 10-13 years old, while the novel model was used with 9-11 year olds only. Across both models and age bands, an older BrainAGE was related to more advanced pubertal development. The relationship between BrainAGE and cognition was less clear, with conflicting relationships across the two models. Additionally, longitudinal analysis revealed moderate to high stability in BrainAGE across early adolescence. The results of the current study provide initial evidence that BrainAGE tracks with some metrics of maturation, including pubertal development. However, the conflicting results between BrainAGE and cognition lead us to question the utility of these models for non-biological processes.

neuroscience↗

bioRxiv2022

Profiling intra- and inter-individual differences in child and adolescent brain development

As we move toward population-level developmental neuroscience, understanding intra- and inter-individual variability in brain maturation and sources of neurodevelopmental heterogeneity becomes paramount. Large-scale, longitudinal neuroimaging studies have uncovered group-level neurodevelopmental trajectories, and while recent work has begun to untangle intra- and inter-individual differences, they remain largely unclear. Here, we aim to quantify both intra- and inter-individual variability across facets of neurodevelopment across early adolescence (ages 8.92 to 13.83 years) in the Adolescent Brain Cognitive Development (ABCD) Study and examine inter-individual variability as a function of age, sex, and puberty. Our results provide novel insight into differences in annualized percent change in macrostructure, microstructure, and functional brain development from ages 9-13 years old. These findings reveal moderate age-related intra-individual change, but age-related differences in inter-individual variability only in a few measures of cortical macro- and microstructure development. Greater inter-individual variability in brain development were seen in mid-pubertal individuals, except for a few aspects of white matter development that were more variable between prepubertal individuals in some tracts. Although both sexes contributed to inter-individual differences in macrostructure and functional development in a few regions of the brain, we found limited support for hypotheses regarding greater male-than-female variability. This work highlights pockets of individual variability across facets of early adolescent brain development, while also highlighting regional differences in heterogeneity to facilitate future investigations in quantifying and probing nuances in normative development, and deviations therefrom.

neuroscience↗

bioRxiv2021

Individual variability in structural brain development from late childhood to young adulthood

A fundamental task in neuroscience is to characterize the brains developmental course. While replicable group-level models of structural brain development from childhood to adulthood have recently been identified, we have yet to quantify and understand individual differences in structural brain development. The present study examined individual variability and sex differences in changes in brain structure, as assessed by anatomical MRI, across ages 8.0-26.0 years in 269 participants (149 females) with three time points of data (807 scans), drawn from three longitudinal datasets collected in the Netherlands, Norway, and USA. We further investigated the relationship between overall brain size and developmental changes, as well as how females and males differed in change variability across development. There was considerable individual variability in the magnitude of changes observed for all included brain measures. However, distinct developmental patterns of change were observed for total brain and cortical gray matter, cortical thickness, and white matter surface area, with individuals demonstrating either stability or decreases in early adolescence, then almost universal decreases during mid-to-late adolescence, before returning to more variable patterns in early adulthood. White matter volume demonstrated a similar developmental pattern of variability, but with individuals shifting from increases to a majority stabilizing during mid-to-late adolescence. We observed sex differences in these patterns, and also an association between an individuals brain size and their overall rate of change. The present study provides new insight as to the amount of individual variance in changes in structural morphometrics from late childhood to early adulthood in order to obtain a more nuanced picture of brain development. The observed individual- and sex-differences in brain changes also highlight the importance of further studying individual variation in developmental patterns in healthy, at-risk, and clinical populations.

neuroscience↗

bioRxiv2020

Downtown Diet: a global meta-analysis of urbanization on consumption patterns of vertebrate predators

Predation is a fundamental ecological process that shapes communities and drives long-term evolutionary dynamics. As the world rapidly urbanizes, it is critical to understand how the built environment and other human perturbations alter predation across taxa. We conducted a meta-analysis to quantify the effects of urban environments on three components of trophic ecology in predators: dietary species richness (DSR), dietary evenness (DEV), and stable isotopic ratios ({delta}13C and {delta}15N IR). We then evaluated whether intensity of anthropogenic pressure, using the human footprint index (HFI), explained variation in the effect sizes of dietary attributes using a meta-regression. We calculated Hedges g effect sizes from 44 studies including 11,986 samples across 40 predatory species in 39 cities globally. The direction and magnitude of effect sizes varied between predator taxonomic groups with reptile diets exhibiting the most sensitivity to urbanization. Effect sizes revealed that predators in cities had comparable DSR, DEV, and nitrogen ratios, though carbon consumption was significantly higher. We found that HFI did not explain variation in effect sizes, a result consistent between the 1993 and 2009 editions of this metric. Our study provides the first assessment of how urbanization has perturbed predator-prey interactions for multiple taxa at a global scale, revealing that the functional role of predators is conserved in cities and urbanization does not inherently relax predation.

ecology↗

bioRxiv2020

An Organotypic Mammary Duct Model Capturing Distinct Events of DCIS Progression

Ductal carcinoma in situ (DCIS) is a pre-cancerous stage breast cancer, where abnormal cells are contained within the duct, but have not invaded into the surrounding tissue. However, only 30-40% of DCIS cases are likely to progress into an invasive ductal carcinoma (IDC), while the remainder are innocuous. Since little is known about what contributes to the transition from DCIS to IDC, clinicians and patients tend to opt for treatment, leading to concerns of overdiagnosis and overtreatment. In vitro models are currently being used to probe how DCIS transitions into IDC, but many models do not take into consideration the macroscopic tissue architecture and the biomechanical properties of the microenvironment. Here, we developed an organotypic mammary duct model by molding a channel within a collagen matrix and lining it with a basement membrane. By adjusting the concentration of collagen, we effectively modulated the stiffness and morphological properties of the matrix and examined how an assortment of breast cells responded to changing density and stiffness of the matrix. We first validated the model using two established, phenotypically divergent breast cancer cell lines by demonstrating the ability of the cells to either invade (MDA-MB-231) or cluster (MCF7). We then examined how cells of the isogenic MCF10 series--spanning the range from healthy to aggressive--behaved within our model and observed distinct characteristics of breast cancer progression such as hyperplasia and invasion, in response to collagen concentration. Our results show that the model can recapitulate different stages of breast cancer progression and that the MCF10 series is adaptable to physiologically relevant in vitro studies, demonstrating the potential of both the model and cell lines to elucidate key factors that may contribute to understanding the transition from DCIS to IDC. IMPACT STATEMENTThe success of early preventative measures for breast cancer has left patients susceptible to overdiagnosis and overtreatment. Limited knowledge of factors driving an invasive transition has inspired the development of in vitro models that accurately capture this phenomenon. However, current models tend to neglect the macroscopic architecture and biomechanical properties of the mammary duct. Here, we introduce an organotypic model that recapitulates the cylindrical geometry of the tissue and the altered stroma seen in tumor microenvironments. Our model was able to capture distinct features associated with breast cancer progression, demonstrating its potential to uncover novel insights into disease progression.

cancer biology↗

bioRxiv2020

Humans induce differential access to prey for large African carnivores

Wildlife adaptively respond to human presence by adjusting their temporal niche, possibly modifying encounter rates among species and trophic dynamics that structure communities. Here we show that these human-induced modifications to behaviours are prolific among species and alter apex predators access to prey resources. We assessed human-induced changes to wildlife diel activity and consequential changes in predator-prey overlap using 11,954 detections of three apex predators and 13 ungulates across 21,430 trap-nights in West Africa. Over two-thirds of species altered their diel use in response to human presence, and ungulate nocturnal activity increased by 6.8%. Rather than traditional pairwise predator-prey comparisons, we considered spatiotemporally explicit predator access to a suite of prey resources to evaluate community-level trophic responses to human presence. Although leopard prey access was not affected, lion and hyena access to 3 prey species significantly increased when prey increased their nocturnal temporal niche to avoid humans. Ultimately, humans considerably altered the composition of available prey, with implications for prey selection, demonstrating how humans perturb ecological processes via behavioural modifications.

ecology↗

bioRxiv2020

Fear not: avoidance behavior missing in species sympatric with the critically endangered West African lion

Predators are major regulators in communities through trophic and non-trophic pathways. However, as human pressures continue to threaten apex predators, including Africas iconic lion, predators functional role in their ecosystems may be compromised. Where lions are critically endangered, we found no evidence of avoidance behavior in either competitor or prey species from a camera survey in the largest protected area complex in West Africa. Our findings raise concerns that lions have already become functionally extinct in portions of their West African range, highlighting the urgency of restorative efforts and environmental investments to reverse current declining population trends and the loss of regulatory roles.

ecology↗

bioRxiv2017

Development of subcortical volumes across adolescence in males and females: A multisample study of longitudinal changes

The developmental patterns of subcortical brain volumes in males and females observed in previous studies have been inconsistent. To help resolve these discrepancies, we examined developmental trajectories using three independent longitudinal samples of participants in the age-span of 8-22 years (total 216 participants and 467 scans). These datasets, including Pittsburgh (PIT; University of Pittsburgh, USA), NeuroCognitive Development (NCD; University of Oslo, Norway), and Orygen Adolescent Development Study (OADS; The University of Melbourne, Australia), span three countries and were analyzed together and in parallel using mixed-effects modeling with both generalized additive models and general linear models. For all regions and across all samples, males were found to have significantly larger volumes as compared to females, and significant sex differences were seen in age trajectories over time. However, direct comparison of sample trajectories and sex differences identified within samples were not consistent. The trajectories for the amygdala, putamen, and nucleus accumbens were most consistent between the three samples. Our results suggest that even after using similar preprocessing and analytic techniques, additional factors, such as image acquisition or sample composition may contribute to some of the discrepancies in sex specific patterns in subcortical brain changes across adolescence, and highlight region-specific variations in congruency of developmental trajectories.

neuroscience↗

bioRxiv2017

Three-dimensional single cell patterning for mid- to high-throughput studies of tumor cell and extracellular matrix heterogeneity

Cancer heterogeneity includes cancer cell genetic heterogeneity and heterogeneity in the tumor microenvironment (TME)--both stromal cells and extracellular matrix (ECM). Determining which combinations of the vast array of possibly interacting heterogeneities drive tumor progression presents a major multi-disciplinary challenge in cancer research. To make effective treatment decisions this challenge must be addressed. The practical challenge is assessing cellular heterogeneity in a statistically powerful way with respect to targeted TME characteristics. Here we present a simple, but extensible, and low-cost method for conducting mid- to high-throughput and long-term studies of heterogeneous cell responses to various biomechanical stimuli in 3D models mimicking the biomechanical properties of the ECM. Using a platform we term \"the drop-patterning chip\" thousands of cells are simultaneously transferred from microwells and fully embedded, only using the force of gravity, in precise patterns in 3D. This method allows for throughputs approaching flow-through methods, which lack phenotypic information on cell-matrix interactions, and does not rely on expensive or harsh patterning forces, which often times also result in a proximal stiff surface.

bioengineering↗

bioRxiv2017

Structural brain development: a review of methodological approaches and best practices

Continued advances in neuroimaging technologies and statistical modelling capabilities have improved our knowledge of structural brain development in children and adolescents. While this has provided an increasingly nuanced understanding of brain development, the field is still plagued by inconsistent findings. This review highlights the methodological diversity in existing longitudinal magnetic resonance imaging (MRI) studies on structural brain development during childhood and adolescence, and addresses how such variation might contribute to inconsistencies in the literature. We discuss the impact of method choices at multiple decision points across the research process, from study design and sample selection, to image processing and statistical analysis. We also highlight the extent to which different methodological considerations have been empirically examined, drawing attention to specific areas that would benefit from future investigation. Where appropriate, we recommend certain best practices that would be beneficial for the field to adopt, including greater completeness and transparency in reporting methods, in order to ultimately develop an accurate and detailed understanding of normative child and adolescent brain development.

scientific communication and education↗