Biology subjects

Day, C.

Publications and source records attributed to Day, C..

4 recordsLinked to original sources

bioRxiv2026

Inexpensive High-Throughput Multiplexed Cytokine Detection for Tuberculosis Diagnostics Using Amplified Enzymatic Metallization

Lack of accurate yet inexpensive diagnostics remains a critical bottleneck in the control and elimination of tuberculosis (TB). Interferon-gamma release assay (IGRA), which involve measurement of the release of the cytokine, interferon-gamma (IFN-{gamma}), in blood samples stimulated with Mycobacterium tuberculosis antigens, is used to detect latent TB infection (LTBI). Use of IGRA in resource-poor settings, in which TB is endemic, is however hindered by the need for specialized equipment for sensitive detection of low amounts of cytokine released. Additionally, recent research has shown the advantage of multiplexed detection of other non-IFN-{gamma} cytokines in improving diagnostic accuracy. However, this requires even more expensive instrumentation and there are no inexpensive or point-of-care compatible multiplexed cytokine detection tools available yet. Here we develop and demonstrate a low-cost, high-throughput, multiplexed cytokine detection platform based on amplified enzymatic silver metallization on a plastic substrate. The assay is performed in microwells formed on a commonly available plastic petri dish and the dry readout of the deposited silver is obtained using a cellphone camera, thus significantly reducing overall cost and complexity of multiplexed cytokine detection. We demonstrate the ability to measure clinically relevant sub-picomolar levels of multiple cytokines, including IFN-{gamma}, interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-) from a small volume (<5{micro}L) of the same blood sample used in an IGRA. Furthermore, we demonstrate the use of this assay to distinguish IGRA+ and IGRA-participant samples from a TB endemic setting.

bioengineering↗

bioRxiv2025

A nutrient bottleneck limits antibiotic efficacy in structured bacterial populations

Antibiotic resistance is a growing global health threat. Therefore, it is critically important to optimize how existing antibiotics act against bacterial infections. Although antibiotic activity is well studied at the single cell level, many infections are caused by spatially structured multicellular populations. In such populations, cellular consumption of scarce nutrients establishes strong spatial variations in their abundance. These nutrient variations have long been hypothesized to help bacterial populations tolerate antibiotics, since single-cell studies show that antibiotic tolerance depends on metabolic activity, and thus, local nutrient availability. Here, we directly test this hypothesis by visualizing cell death in Escherichia coli populations with defined structures upon exposure to nutrient (glucose) and antibiotic (fosfomycin). We find that nutrient availability acts as a bottleneck to antibiotic killing, causing death to propagate through the population as a traveling front--a phenomenon predicted over 20 years ago, but never verified until now. By integrating our measurements with biophysical theory and simulations, we establish quantitative principles that explain how collective nutrient consumption can limit the progression of this "death front," protecting a population from a nominally deadly antibiotic dose. While increasing nutrient supply can overcome this bottleneck, our work reveals that in some cases, excess nutrient can unexpectedly promote the regrowth of resistant cells. Altogether, this work provides a key step toward predicting and controlling antibiotic treatment of spatially structured bacterial populations, yielding fundamental biophysical insights into collective behavior and helping to guide strategies for more effective antibiotic stewardship.

biophysics↗

bioRxiv2019

Lysosomal degradation ensures accurate chromosomal segregation to prevent genomic instability

Lysosomes, as primary degradative organelles, are the end-point of different converging pathways including macroautophagy. To date, lysosome function has mainly focused on interphase cells, while their role during mitosis remains controversial. Mitosis dictates the faithful transmission of genetic material among generations, and perturbations of mitotic division lead to chromosomal instability, a hallmark of cancer. Heretofore, correct mitotic progression relies on the orchestrated degradation of mitotic factors, which was mainly attributed to ubiquitin-triggered proteasome-dependent degradation. Here, we show that mitotic transition does not only rely on proteasome-dependent degradation, as impairment of lysosomes increases mitotic timing and leads to mitotic errors, thus promoting chromosomal instability. Furthermore, we identified several putative lysosomal targets in mitotic cells. Among them, WAPL, a cohesin regulatory protein, emerged as a novel p62-interacting protein for targeted lysosomal degradation. Finally, we characterized an atypical nuclear phenotype, the toroidal nucleus, as a novel biomarker for genotoxic screenings. Our results establish lysosome-dependent degradation as an essential event to prevent genomic instability.

cell biology↗

bioRxiv2019

Neural correlates of the DMT experience as assessed via multivariate EEG

Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience, and particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the relevant subjective experience and thus further our understanding of the neurobiological underpinnings of immersive states of consciousness.

neuroscience↗