Biology subjects

Parker, C.

Publications and source records attributed to Parker, C..

10 recordsLinked to original sources

bioRxiv2026

EEG Oscillations in Guided Mindfulness versus Mind-Wandering in Young Adults: Effects of Auditory Task Instruction and Naturalistic Video

Alpha and theta band EEG oscillations have been implicated in states of mindfulness meditation. However, results are inconsistent and the influence of testing environment variables is not well-characterized. We used EEG to measure the amplitude of brain oscillations in a mindful-attention versus mind-wandering condition, in which guided auditory instructions were interleaved with periods of silence, with and without accompanying naturalistic video projections. We generated precise measures of alpha and theta in a sample of 20 young-adult non-expert meditators, by identifying each participant's individual alpha peak frequency (IAF) from posterior EEG electrodes and using it to define four individualized frequency bands: two low alpha bands (in 2 Hz increments below the IAF), one upper alpha band (from IAF to 2 Hz above IAF), and one theta band (4 Hz - 6 Hz below IAF). We found that the mindfulness manipulation significantly increased power in alpha ranging between 2 Hz below to 2 Hz above IAF, including peak alpha amplitude, compared with mind-wandering. Meanwhile, central theta amplitude was larger when auditory instructions were on versus off, and naturalistic video did not reliably modulate the EEG effects of mindfulness. We conclude that the acute effects of mindfulness in non-expert meditators are most consistently observed as increases of posterior alpha-band activity, and that auditory task-instructions should be accounted for in studies of guided meditation. Observed alpha increases may reflect induced states of calm or relaxation induced by mindfulness practice, as proposed in previous studies. These results may apply to mindfulness training or biofeedback therapies.

neuroscience↗

bioRxiv2026

Prenatal cannabinoid exposure induces sex-specific alterations in placental growth and lipid metabolism gene expression

BackgroundPrenatal cannabis use is becoming increasingly more commonplace. However, cannabis exposure is linked to adverse pregnancy outcomes, including gestational hypertension, preeclampsia, and preterm birth. The aim of this study was to determine the morphological and molecular effects of prenatal cannabinoid exposure on the placenta. MethodsPregnant Sprague-Dawley rats were exposed daily to vaporized THC (100 mg/mL) starting at gestational day (GD)5 until GD19 when dams were sacrificed and fetuses and placentas collected. Fetuses were genotyped for genetic sex and transcriptomic analysis was performed on male and female THC-exposed and control placentas. ResultsOn GD19, both the fetuses and placentas from the THC group were significantly larger than the control. When separated by sex, both male and female THC fetuses were significantly larger; however, only male THC placentas were significantly larger than male control placentas with no significant difference in placental weight between female control and THC placentas. RNA-sequencing revealed enriched biological processes related to nutrient transport and lipid catabolism, protein-lipid complex formation, and lipoprotein particle remodeling and organization. Further transcriptomic analysis determined that the differentially expressed genes and enriched biological processes related to lipid metabolism were preferentially enriched in the female THC placentas compared to the male, suggesting a sex-specific effect. DiscussionCollectively, these data present sex-specific effects of prenatal cannabinoid exposure on placental growth and global gene expression. These data also suggest that sex influences gene expression of genes related to lipid metabolism in the THC-exposed placentas.

Developmental Biology↗

bioRxiv2025

Trophoblast stem cells and syncytiotrophoblasts lack inflammatory responses to LPS but retain robust interferon-mediated antiviral immunity

Early pregnancy requires a tightly regulated pro-inflammatory environment shared between the primitive placenta and decidua. While immune balance supports successful implantation and placental invasion, disruptions in immune signaling during this period can impair implantation and lead to embryo loss. In this study, we investigated the molecular mechanisms underlying immune imbalance during implantation using a trophoblast stem cell (TSC) model. TSCs were cultured in either stem cell or syncytiotrophoblast (STB) differentiation medium and treated with either lipopolysaccharides (LPS) or interferon beta (IFNB). RT-qPCR and Western blotting revealed that LPS failed to induce a pro-inflammatory cytokine response in TSCs or STBs. In contrast, IFNB triggered a strong antiviral response in both TSCs and STBs. RNA-sequencing of IFNB-treated TSC and STB 3D spheroids revealed subtle differences between the TSCs and STB responses to interferons. Both TSC and STB IFNB-treated spheroids mount an interferon-mediated antiviral response; however, STB spheroid genes associated with the type I interferon response, viral RNA/DNA sensing, and antigen processing were upregulated. We also compared the interferon response between the CT27 (female) and CT29 (male) TSCs and STBs. While STBs showed minimal differences, the CT29 TSCs exhibited a markedly stronger interferon response than the CT27 TSCs. Collectively, these findings suggest that the primitive placenta is selectively responsive to interferon signaling rather than direct pathogen-associated stimuli. This implies that maternal immune activation, rather than microbial invasion, likely drives that placental immune response and embryo success at this stage. Understanding these dynamics underscores the importance of the maternal immune balance in early pregnancy success.

developmental biology↗

bioRxiv2025

Ability to predict irregular periods of food deprivation improves body-weight regulation and reduces weight gain in food-insecure starlings

1.Food insecurity is associated with higher body weight in humans and other species, but the causal effect of unpredictable food availability on weight gain is unknown. We measured food intake and weight in starlings (Sturnus vulgaris) exposed to repeated irregular periods of food deprivation. We manipulated the predictability of deprivation between subjects with a 1-hour visual cue that either reliably preceded deprivation (Predictable), or was uncorrelated with deprivation (Unpredictable). During the cue, Predictable birds reduced their food intake and spent less time inactive, indicating that they had learnt the contingency. Despite these responses, they lost less weight during subsequent deprivation. They also ate less and gained less weight when food was returned. Birds with the largest behavioural response to the cue had the lowest overall variance in body weight. Consistent with the insurance hypothesis, food intake and body weight increased over time in both groups and body weight was higher in the Unpredictable group. Our results suggest that when food deprivation was predictable, birds were less reliant on stored fat and instead used conditioned hypometabolism to mitigate the effects of food deprivation. We discuss the implications of our findings for the differential health impacts of food insecurity and intermittent fasting.

animal behavior and cognition↗

bioRxiv2024

Putting computational models of immunity to the test - an invited challenge to predict B. pertussis vaccination outcomes

Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting B. pertussis booster responses and generate experimental data for the explicit purpose of model evaluation. We here describe our second computational prediction challenge using this resource, where we benchmarked 49 algorithms from 53 scientists. We found that the most successful models stood out in their handling of nonlinearities, reducing large feature sets to representative subsets, and advanced data preprocessing. In contrast, we found that models adopted from literature that were developed to predict vaccine antibody responses in other settings performed poorly, reinforcing the need for purpose-built models. Overall, this demonstrates the value of purpose-generated datasets for rigorous and open model evaluations to identify features that improve the reliability and applicability of computational models in vaccine response prediction.

immunology↗

bioRxiv2024

Identifying genomic data use with the Data Citation Explorer

Increases in sequencing capacity, combined with rapid accumulation of publications and associated data resources, have increased the complexity of maintaining associations between literature and genomic data. As the volume of literature and data have exceeded the capacity of manual curation, automated approaches to maintaining and confirming associations among these resources have become necessary. Here we present the Data Citation Explorer (DCE), which discovers literature incorporating genomic data whether or not provenance was clearly indicated. This service provides advantages over manual curation methods including consistent resource coverage, metadata enrichment, documentation of new use cases, and identification of conflicting metadata. The service reduces labor costs associated with manual review, improves the quality of genome metadata maintained by the U.S. Department of Energy Joint Genome Institute (JGI), and increases the number of known publications that incorporate its data products. The DCE facilitates an understanding of JGI impact, improves credit attribution for data generators, and can encourage data sharing by allowing scientists to see how reuse amplifies the impact of their original studies.

genomics↗

bioRxiv2022

Tyrosine kinase inhibitors trigger lysosomal damage-associated cell lysis to activate the NLRP3 inflammasome

Inflammasomes are intracellular protein complexes that control proteolytic maturation and secretion of inflammatory interleukin-1 (IL-1) family cytokines and are thus important in host defense. While some inflammasomes are activated simply by binding to pathogen-derived molecules, others, including those nucleated by NLRP3 and NLRP1, have more complex activation mechanisms that are not fully understood. We screened a library of small molecules to identify new inflammasome activators that might shed light on activation mechanisms. In addition to validating dipeptidyl peptidase (DPP) inhibitors as NLRP1 activators, we find that clinical tyrosine kinase inhibitors (TKIs) including imatinib and masitinib activate the NLRP3 inflammasome. Mechanistically, these TKIs cause lysosomal swelling and damage, leading to cathepsin-mediated destabilization of myeloid cell membranes and cell lysis. This is accompanied by potassium (K+) efflux, which activates NLRP3. Both lytic cell death and NLRP3 activation but not lysosomal damage induced by TKIs are prevented by the cytoprotectant high molecular weight polyethylene glycol (PEG). Our study establishes a screening method that can be expanded for inflammasome research and immunostimulatory drug development, and provides new insight into immunological off-targets that may contribute to efficacy or adverse effects of TKIs. One Sentence SummaryA functional small molecule screen identifies imatinib, masitinib and other tyrosine kinase inhibitors that destabilize myeloid cell lysosomes, leading to cell lysis and K+ efflux-dependent NLRP3 inflammasome activation.

immunology↗

bioRxiv2021

Short senolytic or senostatic interventions rescue progression of radiation-induced frailty and premature ageing in mice

Cancer survivors suffer from progressive frailty, multimorbidity and premature morbidity. We hypothesize that therapy-induced senescence and senescence progression via bystander effects is a significant cause of this premature ageing phenotype. Accordingly, the study addresses the question whether a short anti-senescence intervention is able to block progression of radiation-induced frailty and disability in a pre-clinical setting. Male mice were sub-lethally irradiated at 5 months of age and treated (or not) with either a senolytic drug (Navitoclax or dasatinib + quercetin) for 10 days or with the senostatic metformin for 10 weeks. Follow up was for one year. Treatments commencing within a month after irradiation effectively reduced frailty progression (p<0.05) and improved muscle (p<0.01) and liver (p<0.05) function as well as short-term memory (p<0.05) until advanced age with no need for repeated interventions. Senolytic interventions that started late, after radiation-induced premature frailty was manifest, still had beneficial effects on frailty (p<0.05) and short-term memory (p<0.05). Metformin was similarly effective as senolytics. At therapeutically achievable concentrations metformin acted as a senostatic neither via inhibition of mitochondrial complex I, nor via improvement of mitophagy or mitochondrial function, but by reducing non-mitochondrial ROS production via NOX4 inhibition in senescent cells. Our study suggests that the progression of adverse long-term health and quality-of-life effects of radiation exposure, as experienced by cancer survivors, might be rescued by short-term adjuvant anti-senescence interventions.

cancer biology↗

bioRxiv2021

Loss of BCL-3 sensitises colorectal cancer cells to DNA damage, revealing a role for BCL-3 in double strand break repair by homologous recombination

ObjectiveThe proto-oncogene BCL-3 is upregulated in a subset of colorectal cancers (CRC) and increased expression of the gene correlates with poor patient prognosis. The aim is to investigate whether inhibiting BCL-3 can increase the response to DNA damage in CRC. DesignThe function of BCL-3 in DNA damage response was studied in vitro using siRNA and CRISPR-Cas9 genome editing and in vivo using Bcl3-/- mice. DNA damage induced by {gamma}-irradiation and/or cisplatin was quantified using H2AX and RAD51 foci, repair pathways investigated using HR/NHEJ assays and treatment with the PARP inhibitor olaparib. ResultSuppression of BCL-3 increases double strand break number and decreases homologous recombination in CRC cells, supported by reduced RAD51 foci number and increased sensitivity to PARP inhibition. Importantly, a similar phenotype is seen in Bcl3-/- mice, where the intestinal crypts of these mice exhibit sensitivity to DNA damage and a greater number of double strand breaks compared to wild type mice. Furthermore Apc.Krasmutant x Bcl3-/- mice exhibit increased DNA damage and reduced RAD51+ cells compared to their wild type counterparts when treated with cisplatin. ConclusionThis work identifies BCL-3 as a regulator of the cellular response to DNA damage and suggests that elevated BCL-3 expression could increase resistance of tumour cells to DNA damaging agents including radiotherapy. These findings offer a rationale for targeting BCL-3 in CRC as an adjuvant to conventional therapies and suggest that BCL-3 expression in tumours could be a useful biomarker in stratification of rectal cancer patients for neo-adjuvant chemoradiotherapy.

cancer biology↗

bioRxiv2020

Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells

COVID-19 affects vulnerable populations including elderly individuals and patients with cancer. Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells. ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity. We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells. In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi. In serum-deprived and stimulated cells treated with remdesivir and MEKi we observed correlations between pRB, pERK, and ACE2 expression further supporting role of proliferative state and MAPK pathway in ACE2 regulation. We show elevated cytokines in COVID-19-(+) patient plasma (N=9) versus control (N=11). TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir. We observed MEKi stimulation of NK-cell killing of target-cells, without suppressing TRAIL-mediated cytotoxicity. Pseudotyped SARS-CoV-2 virus with a lentiviral core and SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope infected human bronchial epithelial cells, small airway epithelial cells, or lung cancer cells and MEKi suppressed infectivity of the pseudovirus. We show a drug class-effect with MEKi to stimulate NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells. MEKi may attenuate SARS-CoV-2 infection to allow immune responses and antiviral agents to control disease progression.

cell biology↗