Biology subjects

Bell, K.

Publications and source records attributed to Bell, K..

11 recordsLinked to original sources

bioRxiv2026

Bioprinted Human Primary Arteries Recapitulate Inflammatory Activation and Pharmacologic Rescue

Chronic inflammation drives persistent systemic cytokine signaling that contributes to vascular dysfunction and secondary vasculitis, yet mechanistic studies are limited by models that fail to capture the multicellular architecture and dynamics of human arteries. In contrast, perfusing intact vessels ex vivo has limited tractability because of material availability and difficulty of genetic or biochemical manipulation. We developed a modular, perfused artery-on-a-chip platform by tri-axially bioprinting primary human vascular cells to recapitulate the concentric organization of the intimal, medial, and adventitial layers. The engineered vessels are viable longer than 21 days, with functional endothelial barriers, contractile smooth muscle behavior, and actively remodeled extracellular matrices bearing hallmarks of native vascular tissue. Addition of tumor necrosis factor alpha (TNF) induces altered transcript levels of proinflammatory mediators and secretion of cytokines and matrix-remodeling enzymes without compromising vessel viability. Importantly, this secretory response is effectively attenuated by both a small-molecule JAK1 inhibitor (ABT-317) and anti-TNF antibody (Infliximab), demonstrating the models utility for therapeutic evaluation.

bioengineering↗

bioRxiv2026

Dozens of genetic variants sustain adaptation to urban spatial heterogeneity in Arabidopsis thaliana

Urbanization creates mosaics of microhabitats that sustain diverse plant communities and offer untapped opportunities to understand contemporary ecological and evolutionary processes. Using a city-wide colonization experiment in Cologne (Germany), we identified the environmental factors limiting establishment and persistence of the ruderal species Arabidopsis thaliana and the genetic variants enabling adaptation. We show that standing genetic variation is essential for realizing the species urban niche, enabling rapid adaptation to fine-scale gradients in disturbance, vegetation, and soil conditions. Despite originating from only two parental genotypes, populations evolved substantial adaptive differentiation within three generations, revealing a highly polygenic basis of local adaptation. More broadly, our approach establishes cities as powerful open-air laboratories for uncovering and fostering ecological and evolutionary processes that generate and sustain biodiversity in human-dominated landscapes.

evolutionary biology↗

bioRxiv2026

Overcoming software bottlenecks for scalable passive acoustic monitoring: insights from a global expert assessment

1.Passive acoustic monitoring (PAM) enables non-invasive sampling of wildlife across broad spatial, temporal and taxonomic scales. Its ongoing and widespread use has generated unprecedented volumes of acoustic data, shifting the primary bottleneck from data collection to the storage, processing, integration, and interpretation of PAM outputs. Although many software tools exist to address these challenges, differences in their design, scope, and usability often create fragmented and complex analytical workflows. To identify the key barriers and opportunities shaping the implementation of PAM surveys, we conducted a structured expert solicitation involving 30 international practitioners working across terrestrial and aquatic ecosystems. Experts identified and ranked their most critical pain points in current PAM workflows, spanning data storage, processing, and interpretation. The top challenge identified related to accurate species identification using deep learning and artificial intelligence (AI) models, especially in noisy soundscapes or for underrepresented taxa. Eight additional priority challenges included workflow fragmentation, limited availability of user-friendly analytical and visualisation tools, uneven access to software, manual validation bottlenecks, computational constraints, and difficulties in data handling, standardisation, and sharing. Participants also proposed practical mitigation strategies for these priority challenges, supported by step-by-step guidance to help overcome key barriers. Together, these insights provide a roadmap toward more scalable, open-access, and collaborative software systems, which are increasingly essential to realise the full potential of PAM in global biodiversity monitoring.

ecology↗

bioRxiv2025

Human Mendelian disease and in vivo mutagenesis screening define the molecular architecture of the U8 snoRNA

Over 50 mutations in the vertebrate specific box C/D small nucleolar RNA U8 have been reported to cause leukoencephalopathy with calcifications and cysts (LCC), a progressive cerebral microangiopathy presenting at any age between early infancy and late adulthood. Notably, the majority of these disease-associated mutations are annotated as variants of uncertain significance due to an inability to predict their effect on U8 function. Here, using a zebrafish bioassay, we performed in vivo mutagenesis screening to explore the molecular pathology of LCC. We demonstrate that LCC-associated mutations cluster in function and molecular behaviour according to distinct structural domains within U8, differentially impairing U8 processing, activity and stability. Further, we show that when U8 function is hypomorphic, exogenous human U8 and the endogenous zebrafish U8.3 paralogue increase in stability through a newly discovered post-transcriptional mechanism. This latter response is compromised in patients with LCC due to the presence of a common polymorphism of an N6-methyladenosine modified nucleotide, which we predict to impact disease penetrance.

neuroscience↗

bioRxiv2024

Land-use changes impact root-fungal network connectivity in a global biodiversity hotspot

O_LICross-kingdom associations play a fundamental role in ecological processes. Yet our understanding of plant-fungal co-occurrences in tropical rainforests and the potential impacts of land-use change shaping species connections remains limited. C_LIO_LIBy using amplicon sequencing on DNA from roots and their associated fungal communities, we aim to understand the impact of rainforest transformation on the composition and structure of root-fungal ecological networks in human-modified landscapes in Sumatra, Indonesia. C_LIO_LIEach land-use type supports a distinctive set of indicator species, which are organisms that reflect specific environmental conditions and can signal changes in ecosystem health. We observed a decline in the richness of plant species indicators and plant-fungal associations with increasing land-use intensification. Additionally, there is a turnover in root communities, shifting from native and endemic species in rainforests to non-native, generalist herbaceous species in rubber and oil palm plantations. C_LIO_LIPlant-fungal connectivity significantly declined with increasing land-use intensification, suggesting that managed ecosystems may have weakened root-fungal interactions. Network analysis highlights the distinct responses of various fungal groups. For instance, arbuscular mycorrhizal fungi (AMF) showed fewer connections with modules linked to oil palm and rubber roots, indicating weakened root-fungal associations in monocultures. This aligns with the observed reduction in AMF diversity in converted land-use areas compared to forests, further reinforcing the negative impact of land-use practices in oil palm and rubber monocultures on AMF diversity. C_LIO_LISynthesis. Dimensioning the impacts of rainforest transformations belowground is constrained by our understanding of fungal functional guilds. Highly modified systems exhibited fewer connections, suggesting a dynamic restructuring of root-fungal relationships in response to land-use changes. Understanding the intricate interplay between plants and fungi in the face of land-use change can provide valuable information for conservation efforts, agricultural practices, and ecosystem management strategies aimed at promoting biodiversity, soil health, and ecosystem resilience in the context of changing environmental conditions. Moreover, it underscores the importance of communities networks in land-use planning and management decisions to support plant and fungal diversity in terrestrial ecosystems. C_LI

ecology↗

bioRxiv2024

Worldwide study of the taste of bitter medicines and their modifiers

The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canada immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for two of the five drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in one bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad- tasting medicines to meet the needs of those most sensitive to them.

physiology↗

bioRxiv2023

Direct measures of liking and intensity of taste, smell, and chemesthetic stimuli are similar between young people reporting they did or did not have COVID-19

The recovery period from post-COVID-19 smell and taste dysfunctions varies substantially, lasting from a few days to over a year. We aimed to assess the impact of COVID-19 on post-COVID-19 chemosensory sensitivity in a group of young convalescents of eastern/central European ancestry. We measured subjects smell and taste capabilities with a standard testing kit, Monell Flavor Quiz (MFQ), and collected surveys on COVID-19 history. During testing, subjects rated liking and intensity of six odor samples (galaxolide, guaiacol, beta-ionone, trimethylamine, phenylethyl alcohol, 2-ethyl fenchol) and six taste samples (sucralose, sodium chloride, citric acid, phenylthiocarbamide, menthol, capsaicin) on a scale from 1 (dislike extremely, or no intensity) to 9 (like extremely, or extremely intense). There was no statistical difference in intensity ratings or liking of any sample between subjects who reported a history of COVID-19 (n = 34) and those reporting no history (n = 40), independent of presence/absence or severity of smell/taste impairments (P > 0.05). Additionally, neither vaccination status (full vaccination or no vaccination) nor time from the COVID-19 onset (2-27 months) correlated with liking or intensity. These results suggest that most young adults who had COVID-19 recovered their sense of smell and taste.

physiology↗

bioRxiv2023

Thiazolidinediones are partially effective bitter blockers

PurposeThe bad bitter taste of some medicines is a barrier to overcoming non-compliance with medication use, especially life-saving drugs given to children and the elderly. Here we evaluated a new class of bitter blockers (thiazolidinediones; TZDs). MethodsIn this study, two TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with two separate taste panels: a general panel (N=97, 20-23 yrs, 82.5% female, all Eastern European) and a genetically informative panel (N=158, including 68 twin pairs, 18-82 yrs, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale. FindingsParticipants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the two panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD. ImplicationsThese results suggest that TZDs are partially effective bitter blockers, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use.

physiology↗

bioRxiv2021

Autogenous and anautogenous Culex pipiens bioforms exhibit insulin-like peptide signaling pathway gene expression differences that are not dependent upon larval nutrition

Culex pipiens form pipiens and Cx. pipiens form molestus differ in their ability to produce eggs without a bloodmeal. Autogenous mosquitoes, such as the molestus bioform of Cx. pipiens, depend on nutrition acquired as larvae instead of a bloodmeal to fuel the energy intensive process of vitellogenesis, which requires abundant production of yolk proteins. In anautogenous mosquito systems, ovary ecdysteroidogenic hormone (OEH) and insulin-like peptides (ILPs) transduce nutritional signals and trigger egg maturation in response to a bloodmeal. It is unclear to what extent the process is conserved in autogenous mosquitoes and how the bloodmeal trigger has been replaced by teneral reserves. Here, we measured the effects of a series of nutritional regimens on autogeny, time to pupation, and survival in Cx. pipiens form molestus and form pipiens. We find that abundant nutrients never result in autogenous form pipiens and extremely poor food availability rarely eliminates autogeny from form molestus. However, the number of autogenous eggs generated increases with nutrient availability. Similarly, using qPCR to quantify gene expression, we find several differences in the expression levels of ilps between bioforms that are reduced and delayed by poor nutrition, but not extinguished. Changes in OEH expression do not explain bioform-specific differences in autogeny. Surprisingly, the source of most of the gene expression differences correlated with autogeny is the abdomen, not the brain. Overall, our results suggest that autogeny is modulated by nutritional availability, but the trait is encoded by genetic differences between forms and these impact the expression of ILPs.

evolutionary biology↗

bioRxiv2019

Persistent Cyfip1 expression is required to maintain the adult subventricular zone neurogenic niche

Neural stem cells (NSCs) persist throughout life in the subventricular zone (SVZ) niche of the lateral ventricles as B1 cells. Maintaining this population of NSCs depends on the balance between quiescence and self-renewing or self-depleting proliferation. Interactions between B1 cells and the surrounding niche are important in regulating this balance, but the mechanisms governing these processes have not been fully elucidated in adult mammals. The cytoplasmic FMRP-interacting protein (CYFIP1) regulates apical-basal polarity in the embryonic brain. Loss of Cyfip1 during embryonic development in mice disrupts the embryonic niche and affects cortical neurogenesis. However, a direct role for Cyfip1 in the regulation of adult NSCs has not been established. Here, we demonstrate that Cyfip1 expression is preferentially localized to B1 cells in the adult SVZ. Loss of Cyfip1 in the embryonic mouse brain results in altered adult SVZ architecture and expansion of the adult B1 cell population at the ventricular surface. Furthermore, acute deletion of Cyfip1 in adult NSCs results in a rapid change in adherens junction proteins as well as increased proliferation and the number of B1 cells at the ventricular surface. Together, these data indicate that CYFIP1 plays a critical role in the formation and maintenance of the adult SVZ niche and, furthermore, deletion of Cyfip1 unleashes the capacity of adult B1 cells for symmetric renewal to increase the adult NSC pool.\n\nSIGNIFICANCENeural stem cells (NSCs) persist in the subventricular zone (SVZ) of the lateral ventricles in adult mammals and their population is determined by the balance between quiescence and self-depleting or renewing cell division. The mechanisms regulating their biology are not fully understood. This study establishes that the cytoplasmic FMRP interacting protein 1 (Cyfip1) regulates NSC fate decisions in the adult SVZ and NSCs that are quiescent or typically undergo self-depleting divisions retain the ability to self-renew in the adult. This contributes to our understanding of how adult NSCs are regulated throughout life and has potential implications for human brain disorders.

developmental biology↗

bioRxiv2019

Plasmid transmitted small multidrug resistant (SMR) efflux pumps differ in gene regulation and enhance tolerance to quaternary ammonium compounds (QAC) when grown as biofilms

Small multidrug resistance (SMR) efflux pump genes are commonly identified from integrons carried by multidrug-resistant (MDR) plasmids. SMR pumps are annotated as qac for their ability to confer resistance to quaternary ammonium compounds (QACs) but few qac are characterized to date. Hence, we have examined SMR sequence diversity, antimicrobial susceptibility, and gene expression from >500 sequenced proteobacterial plasmids. SMR sequence diversity from plasmid database surveys identified 20 unique SMR sequences annotated as qacE/E{Delta}1/F/G/H/I/L, or sugE. Phylogenetic analysis shows Qac sequences are homologous to archetypical SMR member EmrE, and share a single sequence origin. In contrast, SugE sequences are homologous to archetypical member Gdx/SugE and likely originate from different species. SMR genes, qacE, qacE{Delta}1, qacF, qacG, qacH, and sugE(p), were over-expressed in Escherichia coli to determine their QAC antimicrobial susceptibility as planktonic, colony, and biofilms. SMRs (except qacE{Delta}1/sugE) expressed in biofilms significantly increased its QAC tolerance as compared to planktonic and colony growth. Analysis of upstream SMR nucleotide regions indicate sugE(p) genes are regulated by type II guanidinium riboswitches, whereas qacE and qacE{Delta}1 have a conserved class I integron Pq promoter, and qacF/G/H are regulated by integron Pc promoter in variable cassettes region. Beta-galactosidase assays were used to characterize growth conditions regulating Pq and Pc promoters and revealed that Pq and Pc have different expression profiles during heat, peroxide, and QAC exposure. Altogether, this study reveals that biofilm growth methods are optimal for SMR-mediated QAC susceptibility testing and suggests SMR gene regulation on plasmids is similar to chromosomally inherited SMR members.

microbiology↗