Biology subjects

Prince, J.

Publications and source records attributed to Prince, J..

10 recordsLinked to original sources

bioRxiv2026

Nanocellulose hydrogels as bio-interface analogs for studying nanomaterial transport and accumulation

Nanomaterials have been proposed as drug delivery vehicles to enhance targeting and efficiency of traditional and novel therapeutics and have subsequently been studied for potential ecotoxicity. Previous studies have identified size, surface charge, and volume exclusion as factors that influence nanomaterial diffusion and retention. However, there is little accepted or successful quantification of how these parameters influence nanomaterial penetration relative to biological adaptation and biological response. Part of the challenge is the response of living biological interfaces to many of these nanomaterial delivery vehicles and nanosized drugs. This study aimed to emulate key physicochemical barriers to diffusion found in living biomaterials by developing a tunable, synthetic hydrogel. Through the controlled exposure of 150 kDa and 2 MDa nanodextrans with neutral and negative surface charge, we evaluated the systems ability to emulate three core physicochemical features often implicated in biofilm-associated transport resistance: size exclusion, charge interactions, and volume exclusion. We demonstrated a 30% statistically significant decrease in partition coefficients for 2 MDa nanodextran from 150 kDa nanodextran, confirming the ability of the nanocellulose-based microcaps to mimic the permeability of hydrated biomaterial matrices. These findings reflect patterns observed in, for example, living biofilm studies, where size-based diffusion hinderance is commonly reported, but charge-based interaction and volume exclusion are more context-dependent. This controllable system can be coupled with in silico modeling to understand interfacial transport phenomena for nanomaterial-biomaterial interactions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/703274v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@13c1a34org.highwire.dtl.DTLVardef@dc6c5borg.highwire.dtl.DTLVardef@14dcbd4org.highwire.dtl.DTLVardef@80f70c_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2026

In vitro evaluation of Escherichia coli and Staphylococcus aureus translocation in 3D printed material

Vascular graft infection is a rare but life threating condition, primarily occurring after 30 days post-surgery. Meta-analysis has shown that antimicrobial coatings on graft materials do not prevent these infections. Moreover, infection still occurs even though studies have also shown that there is no bacterial proliferation on or bacterial penetration of common vascular graft material. The time frame of infection, meta-analysis, and in situ studies suggest that bacteria present at the suture site are introduced into the surrounding tissue or that systemically circulating bacteria may be surviving, proliferating, diffusing slowly, and evading host immune defense in synthetic vascular grafts. De novo vascular graft materials, such as tissue-engineered vascular graft material and decellularized vasculature may provide an in situ platform for studying survival, proliferation, and diffusion in tissue and tissue-like materials. In this study, we use confocal microscopy to image penetration depth of bacteria over time as a proxy for diffusion of Staphylococcus aureus and Escherichia coli into alginate, GelMA, and decellularized porcine vascular tissue. We quantified viable bacteria breakthrough as a function of biomaterial type. We found penetration depth over time was similar in all three biomaterials, however E. coli broke through much less from tissue than from engineered materials, while S. aureus had higher breakthrough in the GelMa but otherwise equal rates. These results point to the possibility of interstitial growth control relative to surface coatings as a future target for engineering infection resistance in engineered vascular grafts. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/703277v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@193760org.highwire.dtl.DTLVardef@1829d6corg.highwire.dtl.DTLVardef@2d4535org.highwire.dtl.DTLVardef@1ab869_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Heterogenous Biofilm Mass-Transport Model Replicates Periphery Sequestration of Antibiotics in P. aeruginosa PAO1 Microcolonies

1A spatiotemporal model for antibiotic accumulation in bacterial biofilm microcolonies which leverages heterogenous porosity and attachment site profiles replicated the periphery sequestration phenomena reported in prior experimental studies on Pseudomonas aeruginosa PAO1 biofilm cell clusters. These P. aeruginosa cell clusters are in vitro models of the chronic P. aeruginosa infections found in adult cystic fibrosis patients, which display resistance to antibiotic treatments, leading to exacerbated morbidity and mortality. This resistance has been partially attributed to periphery sequestration, where antibiotics are unable to penetrate biofilm cell clusters. The underlying physical phenomena driving this periphery sequestration have not been definitively established. This paper introduces mathematical models to account for two proposed physical phenomena driving periphery sequestration: biofilm matrix attachment and volume-exclusion due to variable biofilm porosity. An antibiotic accumulation model which incorporated these phenomena was able to better fit observed periphery sequestration data compared to previous models.

biophysics↗

bioRxiv2022

Measurement of Cervical Neuronal Activity during Stress Challenge Using Novel Flexible Adhesive Surface Electrodes

This study introduces a flexible, adhesive-integrated electrode array that was developed to enable non-invasive monitoring of cervical nerve activity. The device uses silver-silver chloride as the electrode material of choice and combines it with a novel electrode array consisting of a customized biopotential data acquisition unit and integrated graphical user interface (GUI) for visualization of real-time monitoring. Preliminary testing demonstrated this novel electrode design can achieve a high signal to noise ratio during cervical neural recordings. To demonstrate the capability of the surface electrodes to detect changes in cervical neuronal activity, the cold-pressor test (CPT) and a timed respiratory challenge were employed as stressors to the autonomic nervous system. This sensor system recording, a new novel technique, was termed Cervical Electroneurography (CEN). By applying a custom spike sorting algorithm to the novel electrode measurements, neural activity was classified in two ways: 1) pre-to-post CPT, and 2) during a timed respiratory challenge. Unique to this work: 1) rostral to caudal channel position-specific (cephalad to caudal) firing patterns and 2) cross challenge biotype-specific change in average CEN firing, were observed with both CPT and the timed respiratory challenge. Future work is planned to develop an ambulatory CEN recording device that could provide immediate notification of autonomic nervous system activity changes that might indicate autonomic dysregulation in healthy subjects and clinical disease states.

physiology↗

bioRxiv2021

Stratification of Risk of Progression to Colectomy in Ulcerative Colitis using Measured and Predicted Gene Expression

An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of ulcerative colitis (UC) patients require colectomy within five years of diagnosis, but polygenic risk scores (PRS) utilizing findings from GWAS are unable to provide meaningful prediction of this adverse status. By contrast, in Crohns disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a Transcriptional Risk Score (TRS). Here we demonstrate that both measured (TRS) and polygenic predicted gene expression (PPTRS) identify UC patients at 5-fold elevated risk of colectomy with data from the PROTECT clinical trial and UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with transcriptome-wide association studies to stratify risk of disease complications.

genetics↗

bioRxiv2021

Increasing age is independently associated with higher free water in non-active MS brain - A multi-compartment analysis using FAST-T2

PurposeTo explore the relationship between the cerebral cortical perivascular space (PVS) and aging in non-active MS subjects by using the multi-echo T2 relaxometry based cerebrospinal fluid fraction (CSFF) map. MethodsMulti-echo spiral T2 data from 111 subjects with non-active multiple sclerosis (MS) were retrospectively investigated by fitting the T2 data into a three-compartment model, the three water compartments including myelin water, intra-extracellular water, and cerebrospinal fluid. Segmentation of T1w image was performed to get the region of interest (ROI) in cerebral cortical regions. The white matter lesion segmentation was conducted using a convolutional neural network (CNN) based segmentation tool. The CSFF in the ROIs were correlated with age by controlling the gender, white matter hyperintensity lesion burden, and MS disease duration. Multiple linear models were created for the analysis of aging effect on the CSFF. ResultsThe ROI analysis shows that the CSFF in the cerebral cortical regions (temporal, occipital, parietal, front, hippo, and mtl) are significantly linear increasing with age (p<0.01). The intra-extracellular water fraction (IEWF) in the ROIs are significantly linear decreasing (p<0.01). ConclusionThe multi-echo T2 based three-compartment model can be used to quantify the CSFF. The linear increase of CSF water contents in the cerebral cortical regions indicates increased perivascular space load in cortex with aging. The quantification of CSFF may provide a way to understand the glymphatic clearance function in aging and neurodegenerations. HighlightsO_LIMR T2 relaxometry is a valid method to quantify the cerebrospinal fluid fraction (CSFF) in cerebral cortical regions C_LIO_LIThe CSFF in the cerebral cortical regions are positively correlated with age by controlling the white matter lesion load in non-active MS subjects. C_LIO_LIQuantification of cerebral CSFF may reflect the perivascular space load in cortex and better interpret the disease progression in neurodegenerative disease, such as MS. C_LI

neuroscience↗

bioRxiv2020

Methylation Quantitative Trait Loci are Largely Consistent across Disease States in Crohns disease

BackgroundIn a recent study, we identified 1189 CpG sites whose DNA methylation (DNAm) level in blood distinguished Crohns disease (CD) cases from controls. We also demonstrated that the vast majority of these differences were a consequence of disease, rather than a cause of CD. Since methylation can be influenced by both genetic and environmental factors, here we focus on CpGs under demonstrable genetic control (methylation quantitative trait loci, or mQTLs). By comparing mQTL patterns across disease states and tissue (blood vs. ileum), we may distinguish patterns unique to CD. Such DNAm patterns may be relevant for the developmental origins of CD. MethodsWe investigated three datasets: (i) 402 blood samples from 164 newly diagnosed pediatric CD patients taken at two time points, and 74 non-IBD controls (ii) 780 blood samples from a non-CD adult population and (iii) 40 ileal biopsies (17 CD cases and 23 non-IBD controls) from group (i). Genome-wide DNAm profiling and genotyping were performed using the Illumina MethylationEPIC and Illumina Multi-Ethnic arrays. SNP-CpG associations were tested via linear models adjusted for age, gender, disease status, disease subtype, estimated cell type and three genotype-based principal components. We used a Bonferroni-adjusted significance threshold to identify significantly associated SNP-CpG pairs, but also considered larger sets identified by a false discovery rate criterion ResultsIn total, we observed 535,448 SNP-CpG associations between 287,881 SNPs and 12,843 CpG sites (P<8.21x10-14). These associations and their effects are highly consistent across different ages, races, disease states, and tissue types, suggesting that the vast majority of these mQTLs participate in common gene regulation. However, genes near CpGs associated with IBD SNPs were enriched for 18 KEGG pathways relevant to IBD-linked immune function and inflammatory responses. We observed suggestive evidence for a small number of tissue-specific associations and disease-specific ileal associations in ileum, though larger studies will be needed to confirm these results. ConclusionThe vast majority of blood derived mQTLs are commonly shared across individuals. However, we have identified a subset of such, which may be involved in processes related to CD. Independent cohort studies will be required to validate these findings.

genomics↗

bioRxiv2020

Identifying Neural Signatures Mediating Behavioral Symptoms and Psychosis Onset: High-Dimensional Whole Brain Functional Mediation Analysis

Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an brain atlas and a {beta} brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify the P mediators and the N mediators that respectively facilitate or protect against developing brain disorders among subjects with more severe behavioral symptoms and quantify the effect of each neural mediator on disease development. Taken together, the -{beta} atlases and the P-N mediators paint a brain-wide picture of neural markers that are potentially regulating behavioral symptoms and the development of psychotic disorders and highlight a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological organization.

bioinformatics↗

bioRxiv2019

Heart rate variability as an indicator of autonomic nervous system disturbance in tetanus

Autonomic nervous system dysfunction (ANSD) is a significant cause of mortality in tetanus. Currently diagnosis relies on non-specific clinical signs. Heart rate variability (HRV) may indicate underlying autonomic nervous system activity and represents a potentially valuable non-invasive tool for ANSD diagnosis in tetanus. HRV was measured from 3 5-minute ECG recordings during a 24-hour period in a cohort patients with severe tetanus, all receiving mechanical ventilation. HRV measurements from all subjects - 5 with ANSD (Ablett Grade 4) and 4 patients without ANSD (Ablett Grade 3) - showed HRV was lower than reported ranges for healthy individuals. Comparing different severities of tetanus, raw data for both time and frequency measurements of HRV were reduced in those with ANSD compared to those without. Differences were statistically significant in all except root mean square standard deviation RMSSD (p=0.07) indicating HRV may be a valuable tool in ANSD diagnosis.

pathology↗

bioRxiv2019

Extracellular CIRP as a Novel Endogenous TREM-1 Ligand to Fuel Inflammation

Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently-discovered damage-associated molecular pattern. Understanding the precise mechanism by which it exacerbates inflammation in sepsis is essential. Here we identified that eCIRP is a new biologically active endogenous ligand of triggering receptor expressed on myeloid cells-1 (TREM-1), fueling inflammation in sepsis and ischemia-reperfusion. Surface plasmon resonance revealed a strong binding affinity between eCIRP and TREM-1, and FRET assay confirmed eCIRPs interaction with TREM-1 in macrophages. TREM-1 inhibition, either by its siRNA or a decoy peptide LP17, dramatically reduced eCIRP-induced inflammation. We developed a novel 7-aa peptide derived from human eCIRP, M3, which blocked the interaction of TREM-1 and eCIRP. M3 suppressed inflammation induced by eCIRP or agonist TREM-1 Ab crosslinking in murine macrophages or human peripheral blood monocytes. M3 also inhibited eCIRP-induced systemic inflammation and tissue injury. Treatment with M3 further protected mice from sepsis and intestinal ischemia-reperfusion, improved acute lung injury, and increased survival. Thus, we have discovered a novel TREM-1 ligand and developed a new peptide M3 to block eCIRP-TREM-1 interaction and improve the outcome of sepsis and sterile inflammation.

immunology↗