Biology subjects

White, D.

Publications and source records attributed to White, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Naturalistic face-directed attention predicts face recognition ability

Recognising people precedes and informs most social interactions, yet it is not clear why individuals differ so markedly in face recognition ability. Exposure-based accounts propose that it is shaped by visual experience with faces, known as 'face diet', but most prior work treats exposure as passively acquired, thereby masking the active and dynamic nature of visual attention in natural settings. Here we examined whether spontaneous attention to faces in everyday environments predicts face recognition ability. Eighty participants wore mobile eye-tracking glasses while walking through a busy university campus and during a face-to-face interaction, before completing standard measures of face recognition ability. Fixations directed to faces showed stable individual differences in both settings. People who looked more at faces scored higher on our composite measure of face recognition ability, and gaze in the two settings predicted ability independently, together accounting for 22% of its variance. These findings suggest that differences in how people actively sample visual information from their environments may be an overlooked source of variance in perceptual expertise.

animal behavior and cognition↗

bioRxiv2026

Enhanced neural encoding of individual exemplars in the Super-Recogniser brain is specific to faces

Super-Recognisers are known for their exceptional ability to encode and remember faces. Recent work has found robust neural codes for face identity in brain activity. Here we test whether the enhanced individuation of face identity in super-recogniser neural codes extends to exemplars from non-face categories. We recorded 64-channel electroencephalography (EEG) as 22 Super-Recognisers and 20 typical recognisers viewed rapid, randomised sequences of faces, dogs, houses, and cars (10 different images of 10 different exemplars per category). Using a neural decoding approach, we found that Super-Recognisers neural responses contained stronger and more temporally sustained information discriminating individual face identities. Moreover, Super-Recognisers displayed increased inter-individual consistency in the organisation of their face-identity representations, suggesting a more stable and/or canonical representational structure in individuals with superior face recognition abilities. Crucially, there was no evidence to suggest that these encoding advantages generalised to non-face categories: neural discrimination of individual dogs, cars, and houses was comparable across groups, and group-differences in inter-subject consistency were evident only for faces. Together, these findings suggest that enhanced perceptual encoding underlying exceptional face recognition is highly category-specific, supporting the view that expertise in this group reflects specialised mechanisms for processing facial identity rather than broadly enhanced visual discrimination capacities.

neuroscience↗

bioRxiv2026

Robust neural face identity codes in the Super-Recogniser brain

Super-Recognisers show exceptional ability in face recognition, providing a natural model of how perceptual systems optimise for individuating visually similar stimuli in variable viewing conditions. However, the neural representations supporting this extreme perceptual expertise are unknown. Here, we tested whether Super-Recognisers (n = 23) differed from typical recognisers (n = 21) in the dimensional organisation of neural face identity coding. We recorded 64-channel electroencephalography while participants viewed random and rapidly-presented sequences containing 10 naturally varying images of 40 unfamiliar identities. Using time-resolved representational similarity analysis we measured the geometry of identity representations, their consistency across observers, and how clearly they specified face identity. Although neural expression of identity information was robust in both groups, we found three key differences between Super-Recognisers and typical recognisers. First, the geometry of face identity representations differed between groups. Second, Super-Recognisers showed greater inter-individual consistency in representational geometry. Third, Super-Recognisers neural signals discriminated between face identities more strongly than those of typical recognisers. Differences in the coding of broader face categories (sex, age, ethnicity) were notably weaker, suggesting that the observed group differences reflected fine-scale differences in identity coding rather than global reshaping of representational geometry. Strikingly, all three differences emerged within a common mid-latency interval ([~]300-500ms), implicating higher-stages of face processing associated with representations that are sensitive to face familiarity and link between perceptual and semantic domains. Together, these findings indicate that individual differences in face recognition ability reflect higher-level differences in neural identity coding, rather than enhanced early sensory processing. Significance statementSuper-Recognisers have an exceptional ability to recognise unfamiliar faces, yet the neural basis of this advantage has remained unclear. We find brain activity expresses the identity of unfamiliar faces more strongly and consistently in Super-Recognisers than typical recognisers. These advantages were specific to individual identity and could not be explained by enhanced encoding of broader facial categories such as sex, age, or ethnicity. Critically, group differences emerged during a mid-latency stage of processing ([~]300-500 ms) associated with higher-level representations that support stable identity coding across variable images. The findings suggest that exceptional face recognition arises from more robust neural representations of individual identity rather than enhanced early visual processing, providing new insight into the neural basis of perceptual expertise.

neuroscience↗

bioRxiv2026

OncoContour: An Interactive Platform for Geographic Visualization and Demographic Analysis of Cancer Incidence.

Cancer incidence varies substantially across geographic regions and demographic groups, yet translating large-scale surveillance datasets into accessible, interpretable visualizations remains a challenge for researchers and public health professionals without computational expertise. We developed OncoContour, an interactive web-based platform that enables geographic visualization and demographic analysis of cancer incidence data through a browser-accessible interface. To demonstrate its capabilities, we analyzed publicly available cancer incidence data from the United States Cancer Statistics database via CDC WONDER, covering five major cancer types across four northeastern U.S. metropolitan statistical areas from 2017 through 2022, supplemented by demographic data from the U.S. Census Bureau American Community Survey. OncoContour integrates population distribution heatmaps, per-capita cancer incidence heatmaps, interactive multi-city temporal trend charts, structured cancer data tables, and demographic visualizations covering race, ethnicity, age, and sex distributions into a single dynamically generated HTML report. The platform is implemented in Python using Flask, Folium, Plotly, and Matplotlib, and is containerized using Docker for reproducible local deployment. Across all four metropolitan areas, breast and prostate cancers accounted for the highest incidence counts over the study period, while a decline in reported cases observed in 2020 is consistent with documented disruptions to cancer screening during the COVID-19 pandemic. By integrating geospatial mapping, temporal analysis, and demographic visualization within a unified, no-code interface, OncoContour aims to support cancer surveillance, epidemiological investigation, and targeted public health planning. OncoContour is freely available at https://github.com/alperuzun/oncocontour_docker.

bioinformatics↗

bioRxiv2025

Direct In-Sample Sequencing of the 3' Transcriptome Expands the Capabilities of Optical Pooled Screens

We present a platform that directly sequences single guide RNAs and endogenous 3'UTRs in fixed cells while simultaneously measuring protein abundance and cellular morphology. We demonstrate platform capability by performing optical pooled screening of CRISPR-perturbed lung cancer cells. This approach unites direct in-sample RNA sequencing with complementary phenotypic readouts, enabling comprehensive, scalable, and functional genomics analyses within a single experiment.

genomics↗

bioRxiv2025

De Novo Design of Miniprotein Inhibitors of Bacterial Adhesins

The rise of multidrug-resistant bacterial infections necessitates the discovery of novel antimicrobial strategies. Here, we show that protein design provides a generalizable means of generating new antimicrobials by neutralizing the function of bacterial adhesins, which are virulence factors critical in host-pathogen interactions. We de novo designed high-affinity miniprotein binders to FimH and Abp chaperone usher pili adhesins from uropathogenic Escherichia coli and Acinetobacter baumannii, respectively, which are implicated in mediating both uncomplicated and catheter-associated urinary tract infections (UTI) responsible for significant morbidity worldwide. The designed antagonists have high specificity and stability, disrupt bacterial recognition of host receptors, block biofilm formation, and are effective in treating and preventing murine models of uncomplicated and catheter- associated UTIs in vivo.

microbiology↗

bioRxiv2025

Mathematical Model for the Progression of Rhegmatogenous Retinal Detachment (RRD)

The separation of the neural layer (NL) and the retinal pigmented epithelium (RPE), referred to as retinal detachment (RD), is a disease of vertebrate eyes affecting nearly twenty eight thousand individuals in the United States annually. The rate at which RD progresses--especially in response to constant eye movement--and the factors influencing this progression remain poorly understood. This lack of quantitative insight contributes to delays in treatment which can lead to permanent vision loss. In this work, we develop a mathematical model to investigate the progression of retinal detachment over two saccadic eye rotation. We explore how various model parameters--describing fluid properties, biomechanical properties of the retina, molecular properties of the bond between the NL and the RPE, as well as geometric and physical properties of the eye--affect disease progression.

biophysics↗

bioRxiv2025

Mitochondrial DNA Mutations Determine Favourable Molecular Responses to Targeted Kinase Inhibitor Therapy and Impair Oxidative Phosphorylation

Somatic mutations in mitochondrial DNA (mtDNA) are not typically considered key oncogenic drivers of cancer, primarily because of a high synonymous to non-synonymous variant ratio. Here, we surveyed 248 matched diagnosis and remission samples from patients with chronic myeloid leukemia (CML) and found a 75% had mitochondrial mutations with a median number of 2 mutations per patient. mtDNA mutations were predominantly non-synonymous, enriched in the D-loop control region, and likely originated from replication and transcriptional errors. Functionally, mtDNA mutations were associated with reduced oxidative phosphorylation (OXPHOS), as measured by Seahorse analyser. This metabolic vulnerability could be phenocopied by treatment with the complex I inhibitor IACS-10759 in combination with the targeted tyrosine kinase inhibitor (TKI) imatinib, which significantly reduced the colony-forming potential of TKI resistant leukemic stem/progenitor cells (LSPCs). Strikingly, we show that mtDNA mutations were associated with increased sensitivity to imatinib therapy in the clinic. Patients with [≥]3 mutations and patients with mutations in the D-loop showed significantly higher cumulative incidence of major molecular response at 24 months (90% vs. 68%, p = 0.004, and 89% vs 68%, p = 0.004 respectively). Single-cell RNA sequencing further revealed enrichment in non-synonymous mtDNA variants in LSPCs from TKI-sensitive patients, while TKI-resistant cells exhibited upregulated gene signatures related to glycerolipid and phospholipid metabolism and mitochondrial biogenesis. Together, our findings demonstrate that mtDNA mutations are key determinants of sensitivity to targeted therapy, rather than oncogenic drivers of leukemogenesis. Mechanistically, non-synonymous mtDNA mutations appear to restrict mitochondrial metabolic plasticity, with widespread implications for precision oncology.

cancer biology↗

bioRxiv2025

Kinetics of de novo Bone and Bone Marrow Niche Formation with Hybrid Click Cryogels

Successful hematopoietic stem cell transplantation (HSCT) critically depends on efficient T cell recovery, which is limited by compromised bone marrow niches following irradiation. While various factors influence the regeneration of bone and bone marrow niches, the dynamics of this process remain elusive. Here, we explore the kinetics of de novo bone and bone marrow development under varying BMP-2 doses, host immune status, and biological sex, using a cryogel of covalently crosslinked alginate and gelatin releasing BMP-2. Bone formation was monitored by ultrasonography and microcomputed tomography (microCT) analysis, while histological analysis provided insights into the relation between mineralized tissue and bone marrow formation. Bone developed within 2-4 weeks, resulting in cortical bone around the cryogels, and a trabecular bone network with hematopoietic tissue within the cryogels. Higher BMP-2 doses significantly accelerated mineralization kinetics and doubled the resident hematopoietic stem cell population. Notably, immunocompromised status delayed niche development by two weeks and reduced hematopoietic stem cells fourfold. We also found that female mice exhibited enhanced niche formation compared to males under the identical conditions. These findings provide insights into the factors that govern the spatiotemporal regulation of bone and bone marrow niche development and establish this hybrid click cryogel system as a promising platform for improving T cell reconstitution in HSCT patients.

bioengineering↗

bioRxiv2024

Mathematical model for rod outer segment dynamics during retinal detachment and reattachment

Retinal detachment (RD) is the separation of the neural layer from the retinal pigmented epithelium thereby preventing the supply of nutrients to the cells within the neural layer of the retina. In vertebrates, primary photoreceptor cells consisting of rods and cones undergo daily renewal of their outer segment through the addition of disc-like structures and shedding of these discs at their distal end. When the retina detaches, the outer segment of these cells begins to degenerate and, if surgical procedures for reattachment are not done promptly, the cells can die and lead to blindness. The precise effect of RD on the renewal process is not well understood. Additionally, a time frame within which reattachment of the retina can restore proper photoreceptor cell function is not known. Focusing on rod cells, we propose a mathematical model to clarify the influence of retinal detachment on the renewal process. Our model simulation and analysis suggest that RD stops or significantly reduces the formation of new discs and that an alternative removal mechanism is needed to explain the observed degeneration during RD. Sensitivity analysis of our model parameters points to the disc removal rate as the key regulator of the critical time within which retinal reattachment can restore proper photoreceptor cell function.

cell biology↗

bioRxiv2023

Overexpression of Rheb, a positive Tor regulator, reveals principles of rod outer segment size control

The outer segment of retinal rod photoreceptors is a highly modified cilium with the typical ciliary microtubular axoneme but additionally there are hundreds of densely packed, stacked, discrete intramembranous discs containing phototransduction machinery. The outer segment is continuously regenerated or renewed throughout the life of the animal through the combined processes of proximal growth and distal shedding. Since the pioneering experiments decades ago that demonstrated the process of rod outer segment renewal very little research has been directed towards understanding mechanistic principles of renewal and homeostasis, and many important questions remain unaddressed. The rod outer segment is a prime example of tight size control that is amenable to experimental and computational analyses. This study uses zebrafish molecular genetics with high resolution imaging, quantitative analyses, and computational modeling to uncover principles that regulate rod outer segment homeostatic length control. By genetically increasing rod outer segment growth, we show that outer segments lengthen and shedding does not accelerate to offset this added growth.

cell biology↗

bioRxiv2022

SAFB associates with nascent RNAs to promote gene expression in mouse embryonic stem cells

Scaffold Attachment Factor B (SAFB) is a conserved RNA Binding Protein (RBP) that is essential for early mammalian development. However, the RNAs that associate with SAFB in mouse embryonic stem cells have not been characterized. Here, we addressed this unknown using RNA-seq and SAFB RNA immunoprecipitation followed by RNA-seq (RIP-seq) in wild-type ESCs and in ESCs in which SAFB and SAFB2 were knocked out. SAFB predominantly associated with introns of protein-coding genes through purine-rich motifs. The transcript most enriched in SAFB association was the lncRNA Malat1, which also contains a purine-rich region in its 5' end. Knockout of SAFB/2 led to down- and upregulation of approximately 1,000 genes associated with multiple biological processes, including genes that are regulated by Polycomb and genes involved in apoptosis, cell division, and cell migration. The spliced and nascent transcripts of many downregulated genes associated with high levels of SAFB in wild-type cells, implying that SAFB binding promotes their expression. Reintroduction of SAFB into double-knockout cells restored gene expression towards wild-type levels, an effect that was again observable at the level of spliced and nascent transcripts. Proteomics analysis revealed a significant enrichment of nuclear speckle-associated and RS-domain containing proteins among SAFB interactors. Our findings suggest that among other potential functions in mouse embryonic stem cells, SAFB promotes the expression of a subset of genes through its ability to bind purine regions in nascent RNA.

molecular biology↗

bioRxiv2021

Nanotrap Particles Improve Nanopore Sequencing of SARS-CoV-2 and Other Respiratory Viruses

Presented here is a magnetic hydrogel particle enabled workflow for capturing and concentrating SARS-CoV-2 from diagnostic remnant swab samples that significantly improves sequencing results using the Oxford Nanopore Technologies MinION sequencing platform. Our approach utilizes a novel affinity-based magnetic hydrogel particle, circumventing low input sample volumes and allowing for both rapid manual and automated high throughput workflows that are compatible with nanopore sequencing. This approach enhances standard RNA extraction protocols, providing up to 40x improvements in viral mapped reads, and improves sequencing coverage by 20-80% from lower titer diagnostic remnant samples. Furthermore, we demonstrate that this approach works for contrived influenza virus and respiratory syncytial virus samples, suggesting that it can be used to identify and improve sequencing results of multiple viruses in VTM samples. These methods can be performed manually or on a KingFisher Apex system.

microbiology↗

bioRxiv2021

Cohesion in male singing behavior predicts group reproductive output in a social songbird

All social groups require organization to function optimally. Group organization is often shaped by social rules, which function to manage conflict, discourage cheating, or promote cooperation1-5. If social rules promote effective social living, then the ability to learn and follow these rules may be expected to influence individual and group-level fitness. However, such links can rarely be tested, due to the complexity of the factors mediating social systems and the difficulty of gathering data across multiple groups. Songbirds offer an opportunity to investigate the link between social rules and reproductive output because most of their social interactions are mediated by song, a well-studied and readily quantifiable behavior6,7. Using observations from 19 groups of brown-headed cowbirds (Molothrus ater) studied across 15 years, we find evidence for a previously undocumented social rule: cohesive group transitions between dominance- and courtship-related singing. Comparing across groups, the degree of cohesion in male singing behavior predicts the reproductive output of their group. Experimental manipulation of group structure via the introduction of juvenile males to captive flocks reduced group cohesion and adult male reproductive success. Taken together, these results demonstrate that cohesion in group behavioral states can affect both individual and group-level reproductive success, suggesting that selection can act not only on individual-level traits, but also on an individuals ability and opportunity to participate effectively in organized social interactions. Social cohesion could therefore be an unappreciated force affecting social evolution in many diverse systems.

evolutionary biology↗

bioRxiv2021

Variation in female songbird state determines signal state needed to evoke copulation

Female preferences for male signals largely determine courtship success. In most songbirds, females control reproduction via the copulation solicitation display (CSD), an innate, stereotyped posture produced in direct response to male displays. In some species, CSD can be elicited under controlled experimental conditions, allowing CSD production to be used as a bioassay for the underlying mechanics of courtship, however historically our ability to measure variability in CSD was limited. Using computer vision approaches to precisely quantify the trajectory of CSD in female brown-headed cowbirds (Molothrus ater), we show that song potency (how often a song elicits CSD) and female responsivity (how likely a female is to produce CSD) each predict whether a female produces CSD in response to a given presentation. Within elicited CSD, potency and responsivity also predict the duration and onset latency of the displays. By modeling and testing two alternative hypotheses of preference formation, we show that changes in response rates are consistent with a shifting receiver response threshold, suggesting that the song quality required to evoke the copulatory posture in a particular female will vary over time. These results establish a novel framework for exploring CSD and emphasize the importance of the internal state of receivers in determining behavioral responses and suggest that female responsivity acts in conjunction with male signal strength to determine the efficacy of male courtship signaling.

animal behavior and cognition↗

bioRxiv2020

Oxylipin metabolism is controlled by mitochondrial b-oxidation during bacterial inflammation.

Oxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial {beta}-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin {beta}-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-{gamma}. Last, dampening oxylipin levels by {beta}-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial {beta}-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.

biochemistry↗

bioRxiv2020

Age structuring and spatial heterogeneity in prion protein gene (PRNP) polymorphism in white-tailed deer

Chronic-wasting disease (CWD) is a prion-derived fatal neurodegenerative disease that has affected wild cervid populations on a global scale. Susceptibility has been linked unambiguously to several amino acid variants within the prion protein gene (PRNP). Quantifying their distribution across landscapes can provide critical information for agencies attempting to adaptively manage CWD. Here we attempt to further define management implications of PRNP polymorphism by quantifying the contemporary geographic distribution (i.e., phylogeography) of PRNP variants in hunter-harvested white-tailed deer (WTD; Odocoileus virginianus, N=1433) distributed across Arkansas (USA), including a focal spot for CWD since detection of the disease in February 2016. Of these, PRNP variants associated with the well-characterized 96S non-synonymous substitution showed a significant increase in relative frequency among older CWD-positive cohorts. We interpreted this pattern as reflective of a longer life expectancy for 96S genotypes in a CWD-endemic region, suggesting either decreased probabilities of infection or reduced disease progression. Other variants showing statistical signatures of potential increased susceptibility, however, seemingly do so as an artefact of population structure. We also showed marked heterogeneity across the landscape in the prevalence of reduced susceptibility genotypes. This may indicate, in turn, that differences in disease susceptibility among WTD in Arkansas are an innate, population-level characteristic that is detectable through phylogeographic analysis.

genetics↗

bioRxiv2020

A rapidly adaptable biomaterial vaccine for SARS-CoV-2

ABSTRACTThe global COVID-19 pandemic motivates accelerated research to develop safe and efficacious vaccines. To address this need, we leveraged a biomaterial vaccine technology that consists of mesoporous silica rods (MSRs) that provide a sustained release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and adjuvants to concentrate and mature antigen-presenting cells at the vaccine site. Here we explored the humoral responses resulting from the use of monophosphoryl lipid A (MPLA) as the adjuvant and SARS-CoV-2 spike proteins S1, S2, the nucleocapsid (N) protein, and receptor binding domain (RBD) as the target antigens. The dose of antigen and impact of pre-manufacturing of vaccines as versus loading antigen just-in-time was explored in these studies. Single shot MSR vaccines induced rapid and robust antibody titers to the presented antigens, even without the use of a boost, and sera from vaccinated animals demonstrated neutralizing activity against a SARS-CoV-2 pseudovirus. Overall, these results suggest the MSR vaccine system may provide potent protective immunity when utilized to present SARS-CoV-2 antigens.Competing Interest StatementThe authors have declared no competing interest.View Full Text

immunology↗