Biology subjects

Mills, L.

Publications and source records attributed to Mills, L..

8 recordsLinked to original sources

bioRxiv2026

Adolescent brain-age differences between profiles based on suicidal ideation, distress and wellbeing

BackgroundPredicted brain-age derived from structural neuroimaging is being increasingly explored as a marker of brain maturation and biological age, with mental ill-health linked to advanced biological ageing in adults. Longitudinal evidence in adolescents remains limited, and the relationship between suicidality, psychological distress, wellbeing and brain-age gap (BrainAGE; predicted brain-age minus chronological age) is poorly understood. MethodsData were drawn from 135 adolescents (54.8% female; 12-16.9 years; n=688 observations) from the Longitudinal Adolescent Brain Study. Latent profile analysis (LPA) used person-level means and standard deviations of distress (K10), wellbeing (COMPAS-W) and suicidal ideation (SIDAS). BrainAGE was estimated using the CentileBrain Global-BrainAGE pipeline from FreeSurfer-derived morphometric features. Associations between cluster membership and BrainAGE were examined using linear regression and linear mixed-effects models, adjusted for chronological age and sex. ResultsThree profiles emerged: low distress (N=110; 50% female), moderate distress with greater suicidal ideation (N=14; 64% female) and moderate distress with lower suicidal ideation (N=11; 91% female). The moderate distress with lower suicidal ideation cluster showed significantly higher BrainAGE relative to the low distress cluster (B=1.87, SE=0.76, p=.015). Whereas, the moderate distress with greater suicidal ideation cluster did not differ to the low distress cluster. Chronological age was positively associated with BrainAGE (B=0.67, SE=0.07, p<.001). ConclusionsDistinct adolescent mental health profiles may be associated with BrainAGE, depending on the levels and stability of distress and suicidality. However, the longitudinal associations were less robust across small extensions of the developmental range studied, warranting some cautious interpretation and need for replication.

neuroscience↗

bioRxiv2025

PBDE flame retardant exposure causes neurobehavioral and transcriptional effects in first-generation but not second-generation offspring fish

Environmental pollutants can have lasting effects that extend beyond the exposure period, potentially impacting multiple generations. Despite the widespread presence of polybrominated diphenyl ether (PBDE) flame retardants in the environment including oceans globally, there is limited understanding of their potential for multigenerational toxicity. We investigated whether exposures to 2,2,4,4,5-pentaBDE (BDE-99), a predominant PBDE congener, can induce neurobehavioral and molecular effects across two generations using the marine vertebrate model fish Fundulus heteroclitus (Atlantic killifish). To assess how exposure route influences outcomes, we conducted two complementary experiments: in the progenitor exposure experiment, adult fish were exposed to BDE-99 through diet, leading to maternal transfer into F1 eggs, while in the direct embryonic exposure experiment, embryos were exposed to BDE-99 via waterborne exposure, achieving comparable embryonic doses. Both exposure routes resulted in altered photomotor responses in F1 larvae, but additional effects differed by exposure route. In the progenitor exposure, maternally exposed F1 juvenile fish exhibited reduced anxiety-like behavior and changes in brain gene expression, while in the direct embryonic exposure, F0 fish showed no detectable effects within their generation but caused behavioral alterations in F1 descendants. The lack of effects in direct F0 individuals suggests that neurobehavioral effects observed in maternally exposed F1 fish were not solely due to BDE-99 transfer but were influenced by additional maternal factors. In the progenitor exposure, neither behavioral nor gene expression effects persisted in the F2 generation. We conclude that maternal influences play a key role in shaping multigenerational effects of BDE-99 exposure, as indicated by the strong effects observed in maternally exposed F1 fish but not in F2 descendants, as well as the differences between maternally exposed fish and those exposed to comparable doses of BDE-99 alone.

pharmacology and toxicology↗

bioRxiv2025

Early-life PBDE flame retardant exposures cause neurobehavioral alterations in fish that persist into adulthood and vary by sex and route of exposure

Developing organisms exhibit varying susceptibility to environmental pollutants depending on the timing of exposure during development. Early-life development is particularly vulnerable, and many marine species spend early life in nearshore environments, elevating their risk of pollutant exposure. Polybrominated diphenyl ether (PBDE) flame retardants are persistent and ubiquitous pollutants, particularly in nearshore marine environments. They disrupt early-life development and pose ongoing risks for ocean health. However, whether early-life exposure influences neurotoxic effects, and whether those effects are durable throughout life, remains poorly understood. Using Fundulus heteroclitus, we tested whether early-life exposure to 2,2,4,4,5-pentaBDE (BDE-99) leads to persistent behavioral and molecular alterations in adulthood and whether outcomes differ by exposure route. We conducted two complementary experiments comparing progenitor (maternal) exposure and direct waterborne exposure during embryonic development. Similar doses to developing fish were achieved in both experiments. After hatch, all fish were reared in clean water until adulthood over two years later, at which time we assessed impacts on behavior and brain gene expression. Both exposure routes led to long-term hyperactivity and reduced anxiety-like behavior, but specific effects varied by dose and sex. Progenitor exposure altered behavior and the brain transcriptome in F1 males (females not tested), whereas direct embryonic exposure affected behavior in females and not males. These findings highlight the importance of maternal influences, such as chemical metabolites, altered lipid provisioning, small molecules, and epigenetic imprinting, alongside chemical transfer, in shaping the long-term persistence of behavioral and molecular effects from early-life exposure. The distinct effects between exposure routes suggest that dosing with chemical alone is not the only determinant of toxicity. We conclude that maternal factors that are modified by exposure significantly contribute to health outcomes in developing offspring, emphasizing the need to consider exposure route when assessing risks from persistent pollutants. Given that maternal and environmental exposures co-occur in nature, future studies should assess their combined impacts to better predict real-world risks.

pharmacology and toxicology↗

bioRxiv2024

Geometric eigenmode brain fingerprinting and its longitudinal associations with adolescent mental health and wellbeing

Background Brain fingerprinting research posits that individual uniqueness can be identified by structural and functional features that may also be linked to mental health outcomes. Global structural features of the brain can be succinctly and directly captured from magnetic resonance imaging (MRI) via the eigenmodes of the cortical surface - known as geometric eigenmodes. This research investigates how the uniqueness of geometric eigenmodes changes across adolescence and their longitudinal relation to mental health and wellbeing. MethodsThe current study utilised n=613 MRI, self-report and demographic datasets from N=116 community-recruited adolescents enrolled in the Longitudinal Adolescent Brain Study (LABS), between the ages of 12-17 years. MPRAGE scans at each participants visit were used to derive 225 left-hemisphere geometric eigenmodes. Eigenmodes were clustered into 14 eigengroups and developmental trajectories of their uniqueness and longitudinal associations with mental wellbeing and psychological distress were examined. ResultsAll eigengroups become significantly more unique longitudinally, and higher mode (shorter wavelength) eigengroups were more unique than lower mode groups in adolescence. Less uniqueness in eigengroup 6 was significantly associated with higher psychological distress and lower mental wellbeing at concurrent and future timepoints. ConclusionGeometric eigengroup brain fingerprinting offers a novel way to examine neurodevelopment. This study provides evidence that eigengroups have distinct trajectories from adolescence to adulthood, consistent with other imaging studies demonstrating increasing uniqueness in this period. Importantly, they are associated with mental health state and thus may represent neurobiological markers for mental illness onset, building on previous LABS research demonstrating that the functional uniqueness of the cognitive control network predicts psychological distress four months later.

neuroscience↗

bioRxiv2023

A Multi-omic and Multi-Species Analysis of Right Ventricular Failure

Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no approved treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Here, we used transcriptomics and proteomics analyses to define the molecular pathways associated with cardiac MRI-derived values of RV hypertrophy, dilation, and dysfunction in pulmonary artery banded (PAB) piglets. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare the three species. Transcriptomic and proteomic analyses identified multiple pathways that were associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the three species. FAO and ETC proteins and transcripts were mostly downregulated in rats, but were predominately upregulated in PAB pigs, which more closely matched the human data. Thus, the pig PAB metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and that pigs more accurately recapitulate the metabolic aspects of human RVF.

biochemistry↗

bioRxiv2023

Microplastics analytics: why we should not underestimate the importance of blank controls

Recent years have seen considerable scientific attention devoted towards documenting the presence of microplastics (MPs) in environmental samples. Due to omnipresence of environmental microplastics, however, disentangling environmental MPs from sample contamination is a challenge. Hence, the environmental (collection site and laboratory) microplastics contamination of samples during processing is a reality that we must address, in order to generate reproducible and reliable data. Here we investigated published literature and have found that around 1/5 of studies failed to use blank controls in their experiments. Additionally, only 34% of the studies used a controlled air environment for their samples processing (laminar flow, fume hood, closed laboratory, clean room, etc.). In that regard, we have also shown that preparing samples in the fume hood, leads to more microplastics contamination than preparing it in the laboratory bench and the laminar flow. Although it did not completely prevent microplastics contamination, the processing of sample inside the laminar flow is the best option to reduce sample contamination during processing. Overall, we showed that blank controls are a must in microplastics sample preparation, but it is often overlooked by researchers. HighlightsO_LIMost of the contaminant microplastics in blank controls were particles < 20 m. C_LIO_LIFume hoods result in more contamination than processing the samples on the bench. C_LIO_LILaminar flow was the best option for reducing MPs contamination of samples. C_LIO_LI1/5 of studies failed to use blank controls, and 1/3 did not correct their data. C_LIO_LIImproving the use and description of blanks is imperative for ensuring data quality. C_LI Mandatory graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/527118v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1de1ef4org.highwire.dtl.DTLVardef@1c240cdorg.highwire.dtl.DTLVardef@2c57bcorg.highwire.dtl.DTLVardef@1341059_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines

IntroductoryThe evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic.

microbiology↗

bioRxiv2020

Validation of a SARS-CoV-2 spike ELISA for use in contact investigations and serosurveillance

Since emergence of SARS-CoV-2 in late 2019, there has been a critical need to understand prevalence, transmission patterns, to calculate the burden of disease and case fatality rates. Molecular diagnostics, the gold standard for identifying viremic cases, are not ideal for determining true case counts and rates of asymptomatic infection. Serological detection of SARS-CoV-2 specific antibodies can contribute to filling these knowledge gaps. In this study, we describe optimization and validation of a SARS-CoV-2-specific-enzyme linked immunosorbent assay (ELISA) using the prefusion-stabilized form of the spike protein [1]. We performed receiver operator characteristic (ROC) analyses to define the specificities and sensitivities of the optimized assay and examined cross reactivity with immune sera from persons confirmed to have had infections with other coronaviruses. These assays will be used to perform contact investigations and to conduct large-scale, cross sectional surveillance to define disease burden in the population.

immunology↗