Biology subjects

Knight, S.

Publications and source records attributed to Knight, S..

6 recordsLinked to original sources

bioRxiv2026

Immuno-Proteomic Age of Cardiovascular Etiology (iPACE) Signature Predicts Cardiovascular Risk in Elderly Patients

Despite advances in clinical care, cardiovascular disease (CVD) remains the leading cause of disability and mortality worldwide. While age alone is a primary risk factor for CVD, accumulating evidence suggests the immune system influences the initiation and progression of CVD pathophysiology, particularly in heart failure with preserved ejection fraction (HFpEF) and atherosclerotic CVD (ASCVD). Here, using two independent cohorts of older adults, we develop a thirty-protein signature of age based on serum immune proteomics, which correlates with HFpEF and ASCVD risk and mortality (Immuno-Proteomic Age of Cardiovascular Etiology, iPACE). We find aging-related circulating immune proteins associated with ASCVD and HFpEF-specific resilience and susceptibility that may be used as potential prognostic, diagnostic, or therapeutic targets.

immunology↗

bioRxiv2026

Relative humidity differentially modulates decay of structurally distinct respiratory viruses in deposited human saliva particles

Respiratory viruses pose a major threat to human health. Environmental virus persistence in respiratory secretions is essential for successful spread, yet studies have focused largely on a select few viruses in non-physiological matrices. Here, we compared the stability of structurally distinct human respiratory viruses, adenovirus, influenza virus, and rhinovirus, in deposited particles of pooled human saliva under indoor-relevant relative humidity (RH) conditions. Adenovirus exhibited <2.2-log10 decay over 6 h regardless of RH, while rhinovirus exhibited significantly greater degradation (>3.8-log10, at 50% and 80% RH). Influenza virus showed minimal decay at 20% and 50% RH but degraded significantly more (3-log10) at 80% RH. To distinguish aspects of human saliva that are key determinants in driving virus decay, we recapitulated saliva composition using the inorganic solute and protein concentrations determined via ion-coupled plasma mass spectrometry and proteomics, respectively. Rhinovirus was significantly more stable in simulated saliva than in human saliva at 50% RH, while influenza virus and adenovirus behaved similarly in both matrices. These findings emphasize virus-specific environmental persistence and highlight limitations of relying on a single virus and particle matrix for defining public health strategies. Ultimately, these insights will contribute to approaches for mitigating environmental transmission of distinct respiratory pathogens.

microbiology↗

bioRxiv2025

Evidence for Toxin-Encoding Coinfections Driving Intransitive Dynamics Between Allelopathic Phenotypes in Natural Yeast Populations

Competitive intransitivity -- non-hierarchical interactions, such as those exemplified by the rock-paper-scissors game, where no single competitor wins outright -- has been proposed as a key mechanism for maintaining biodiversity; however, empirical evidence supporting the importance of intransitivity remains limited. Natural populations of Saccharomyces cerevisiae often include strains harboring totivirus-satellite coinfections that encode a lethal toxic glycoprotein capable of eliminating competing yeast strains. Killer strains are sparsely distributed in natural populations, despite their competitive advantage. Yeast isolates occasionally exhibit toxin resistance, but it remains untested whether they can outcompete and replace killer strains. Similarly, the persistence of toxin-susceptible yeast is not well understood --particularly whether they can invade resistant populations in the absence of killers, thereby completing an intransitive loop. In a multi-year collection of yeast isolates from vineyards across New Zealand, we observed a near-complete disappearance of a previously common killer yeast genotype of S. cerevisiae over consecutive years. Using space-time-shift competition assays, we demonstrate that strains sympatric to this killer genotype were ubiquitously resistant, unlike the allopatric strains that were frequently eliminated in competition assays. Furthermore, the extinction of the focal killer genotype appears to have enabled the emergence of toxin-susceptible competitors in sites formerly occupied by the killer genotype. Our findings suggest that the competitive advantage of toxin production is evident in natural populations but appears to be eroded when resistance evolves in competitors of the focal killer genotype. We suggest that such killer-resistant-susceptible polymorphisms are being maintained by evolutionary dynamics akin to rock-paper-scissors-like intransitivity, driven by the invasion of susceptible strains after costly resistance has driven killer strains to extinction in natural populations, all being driven by toxin-encoding coinfections.

evolutionary biology↗

bioRxiv2025

Loss of Vertically-Inherited Totiviruses and Toxin-Encoding Satellites in Killer Yeast Evidences Intracellular Conflict in Natural Populations

Saccharomyces cerevisiae is occasionally infected by totiviruses and their toxin-encoding satellites. Totiviruses and their satellites coexist but with an asymmetric dependence on the totivirus for maintenance inside the host cell. Satellites provide their yeast hosts with inhibitory toxins and the necessary self-immunity; loss of the satellite equates to loss of immunity. Because mycoviruses lack known extracellular stages, and sex is considered rare, mycoviruses are assumed to be transmitted vertically, implying infection states should correlate with host genotypes. However, totivirus-satellite coinfections are rarely examined in natural populations, leaving their associations with host genotypes poorly understood. We screened a multiyear population of S. cerevisiae isolates from New Zealand to examine the stability of host-virus associations over time, both within and across genotypes. While 55% of wild isolates harbored infections, only 37% of these included toxin-encoding satellites. Genotypes that persisted across years typically maintained consistent infection states. However, we observed stepwise transitions including acquisitions of totiviruses and satellites. Genotypes clustered strongly by infection state, supporting vertical transmission while suggesting that outcrossing is not responsible for the mycovirus acquisitions. Despite infection changes, genotype clustering by infection state remained intact, suggesting transitions are transient and that host genotypes may have optimal totivirus-satellite infection states.

evolutionary biology↗

bioRxiv2023

Theranostic gold in a gold cage nanoparticle for photothermal ablation and photoacoustic imaging of skin and oral infections

AbstractBiofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we describe a unique structure of dextran coated gold in a gold cage nanoparticle that enables photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser can selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observe a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections respectively. These effects were over 100 times greater than that seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We conclude that photothermal ablation using theranostic nanoparticles is a rapid, precise, and non-toxic method to detect and treat biofilm-associated infections.

bioengineering↗

bioRxiv2017

Identification of Novel Breast Tumor Expression Dimensions within the PAM50 and Discovery of a Breast Cancer Susceptibility Locus at 12q15

It is well-known that breast tumors exhibit different expression patterns that can be used to assign intrinsic subtypes - the PAM50 assay, for example, categorizes tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like - yet tumors are often more complex than categorization can describe. We used 911 sporadic breast tumors to reparameterize expression from the PAM50 genes to five orthogonal tumor dimensions using principal components (PC). Three dimensions captured intrinsic subtype, two dimensions were novel, and all replicated in 945 TCGA tumors. By definition dimensions are independent, an important attribute for inclusion in downstream studies exploring effects of tumor diversity. One application where tumor subtyping has failed to provide impact is susceptibility genetics. Germline genetic heterogeneity reduces power for gene-finding. The identification of heritable tumor characteristics has potential to increase homogeneity. We compared 238 breast tumors from high-risk pedigrees not attributable to BRCA1 or BRCA2 to 911 sporadic breast tumors. Two PC dimensions were significantly enriched in the pedigrees (intrinsic subtypes were not). We performed proof-of-concept gene-mapping in one enriched pedigree and identified a 0.5 Mb genomewide significant region at 12q15 that segregated to the 8 breast cancer cases with the most extreme PC tumors through 32 meioses (p=2.6x10-8). In conclusion, our study: suggests a new approach to describe tumor diversity; supports the hypothesis that tumor characteristics are heritable providing new avenues for germline studies; and proposes a new breast cancer locus. Reparameterization of expression patterns may similarly inform other studies attempting to model the effects of tumor heterogeneity.

genetics↗