Biology subjects

McCall, M.

Publications and source records attributed to McCall, M..

7 recordsLinked to original sources

bioRxiv2026

Microfilaremic loiasis is associated with T cell hyporesponsiveness against SARS CoV-2

BackgroundLoiasis is a chronic filarial infection endemic to Central and West Africa. Although long considered benign, increasing evidence links loiasis to substantial morbidity and mortality. The infection is associated with immune modulation, including Th2-skewed responses and elevated regulatory cytokines. Clinically, loiasis is classified as microfilaremic (presence of circulating microfilariae) or amicrofilaremic ("occult") disease, the latter defined by a history of eyeworm migration without detectable microfilaremia. This study investigated how chronic L. loa infection influences antibody and T cell responses to SARS-CoV-2 following natural infection. MethodsBetween 2022 and 2024 this cross-sectional study was done in Lambarene and surrounding rural areas of Gabon. Study procedures included diagnostics for loiasis and immunological assays. Microfilaremia was confirmed by stained blood smear microscopy, and occult disease was identified using the Rapid Assessment Procedure for Loiasis. SARS-CoV-2-specific IgG responses to spike and nucleocapsid proteins were measured by ELISA, and IFN-{gamma} responses to spike antigen were assessed using an interferon-gamma release assay. ResultsOverall, 192 participants were categorized as microfilaremic (n=43), occult loiasis (n=59), or without evidence of active loiasis (n=90). IFN-{gamma} responses were reduced in microfilaremic individuals compared with other participants (p= 0.031), whereas IgG responses did not differ. Subsequent analysis across the three groups confirmed that IFN-{gamma} responses were lower in microfilaremic compared with occult participants (p= 0.012). ConclusionThese findings suggest that microfilaremic loiasis may impair proinflammatory T cell responses to viral antigens, highlighting the need for further research into the broader immunological effects of Loa loa infection in endemic populations. Authors summaryLoiasis is a parasitic infection caused by the worm Loa loa and is common in parts of Central and West Africa. Although long considered relatively benign, growing evidence indicates that loiasis is associated with substantial morbidity. The immunological consequences of chronic Loa loa infection remain poorly understood. A small number of studies suggest that Loa loa may influence immune regulation, but its broader impact on antiviral immunity is largely unknown. The COVID-19 pandemic provided a unique opportunity to examine immune responses to a newly emerging virus in a population where loiasis is endemic. We therefore investigated how different forms of Loa loa infection influence immune responses after natural SARS-CoV-2 infection. We compared individuals with circulating microfilariae in their blood (microfilaremic), individuals with occult loiasis (history of eye worm), and individuals without signs of active infection. We found that microfilaremic individuals had weaker virus-specific IFN-{gamma} T cell responses, while antibody levels were similar across groups. These findings suggest that active loiasis may dampen certain antiviral immune functions. Understanding the underlying mechanisms is important, as such immune modulation could affect responses to vaccines and other infectious diseases in endemic regions.

immunology↗

bioRxiv2024

Root traits and tree functional groups determine variability in root exudation and N uptake rates in mature temperate trees

While root exudation has the potential to affect soil biogeochemistry profoundly, the process is rarely quantified in mature, field-grown trees. We measured rates of carbon (C) exudation in 11 trees species that exhibit divergent root traits, including gymnosperms and angiosperms that associate with either arbuscular mycorrhizal (AM) or ectomycorrhizal (EcM) fungi. Our goal was to explore how tree species, plant functional groups and root traits collectively influence exudation patterns. Intraspecific variation in exudation rates was larger than interspecific variation, and neither functional groups nor morphological traits alone could sufficiently explain variation in this flux. EcM-associated gymnosperms exuded 2.4 times more C than EcM angiosperms and 1.5 times more than AM gymnosperms. Exudation rates correlated positively with specific root length (SRL) and specific root area (SRA), and were correlated with root tissue density and root diameter in EcM-associated species. Mixed-effect models revealed that exudation rates were best determined by a combination of phylogenetic group, tree-mycorrhizal type and SRA, though a large portion of unexplained variation suggests that contemporary environmental and local edaphic conditions are likely important. Collectively, our results reveal that exudation is a complex physiological process governed by multiple factors and cannot be fully explained by functional groups or root traits alone. Instead, a combined consideration of these factors and new experimental approaches may be needed before exudation patterns can be linked to plant trait frameworks and incorporated into large-scale models.

ecology↗

bioRxiv2024

Statistical Modeling for MicroRNA Sequencing Data

MicroRNAs play a central role in regulating gene expression and modulating diseases. Despite the importance of microRNAs, statistical methods for analyzing them have received far less attention compared to messenger RNAs. Commonly, messenger RNA-seq methods are applied to microRNA-seq data, which may produce erroneous results due to the highly competitive nature of microRNA sequencing. This study critically examines and challenges the assumptions of messenger RNA-seq methods when applied to microRNA-seq data. We propose a Negative Binomial Softmax Regression (NBSR) method to model the unique characteristics of microRNA-seq data. On both simulated and experimental datasets, NBSR outperforms existing methods and offers a new perspective for analyzing microRNA-seq data. NBSR is implemented in Python and freely available as open-source software.

bioinformatics↗

bioRxiv2022

Aβ-CT affective touch: Touch pleasantness ratings for gentle stroking and deep pressure exhibit dependence on A-fibers

Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A preference for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway. Recently, ablation of the spinothalamic pathway-thought to convey all C-fiber sensations-in patients with cancer pain impaired pain, temperature, and itch, but not ratings of pleasant touch. This suggested integration of A and CT fiber input in the spinal cord, or A-fiber contributions to computations of touch pleasantness in the brain. However, the causal contribution of A-fibers to touch pleasantness- in humans without pain-remains unknown. In the current, single-blinded study we performed two types of peripheral nerve blocks in healthy adults to temporarily eliminate the contribution of A-fibers to touch perception. Our findings show that when A-fiber function is greatly diminished, the perceived intensity and pleasantness of both gentle stroking and deep pressure are nearly abolished. These findings demonstrate that explicit perception of the pleasantness of CT-targeted brushing and pressure both critically depend on A-fibers.

neuroscience↗

bioRxiv2021

Nuclear Factor I in neurons, glia and during the formation of Muller glia-derived progenitor cells in avian, porcine and primate retinas

The regenerative potential of Muller glia (MG) is extraordinary in fish, poor in chick and terrible in mammals. In the chick model, MG readily reprogram into proliferating Muller glia-derived progenitor cells (MGPCs), but neuronal differentiation is very limited. The factors that suppress the neurogenic potential of MGPCs in the chick are slowly being revealed. Isoforms of Nuclear Factor I (NFI) are cell-intrinsic factors that limit neurogenic potential; these factors are required for the formation of MG in the developing mouse retina (Clark et al., 2019) and deletion of these factors reprograms MG into neuron-like cells in mature mouse retina (Hoang et al., 2020). Accordingly, we sought to characterize the patterns of expression NFIs in the developing, mature and damaged chick retina. In addition, we characterized patterns of expression of NFIs in the retinas of large mammals, pigs and monkeys. Using a combination of single cell RNA-sequencing (scRNA-seq) and immunolabeling we probed for patterns of expression. In embryonic chick, levels of NFIs are very low in early E5 (embryonic day 5) retinal progenitor cells (RPCs), up-regulated in E8 RPCs, further up-regulated in differentiating MG at E12 and E15. NFIs are maintained in mature resting MG, microglia and neurons. Levels of NFIs are reduced in activated MG in retinas treated with NMDA and/or insulin+FGF2, and further down-regulated in proliferating MGPCs. However, levels of NFIs in MGPCs were significantly higher than those seen in RPCs. Immunolabeling for NFIA and NFIB closely matched patterns of expression revealed in different types of retinal neurons and glia, consistent with findings from scRNA-seq. In addition, we find expression of NFIA and NFIB through progenitors in the circumferential marginal zone at the far periphery of the retina. We find similar patterns of expression for NFIs in scRNA-seq databases for pig and monkey retinas. Patterns of expression of NFIA and NFIB were validated with immunofluorescence in pig and monkey retinas wherein these factors were predominantly detected in MG and a few types of inner retinal neurons. In summary, NFIA and NFIB are prominently expressed in developing chick retina and by mature neurons and glia in the retinas of chicks, pigs and monkeys. Although levels of NFIs are decreased in chick, in MGPCs these levels remain higher than those seen in neurogenic RPCs. We propose that the neurogenic potential of MGPCs in the chick retina is suppressed by NFIs.

neuroscience↗

bioRxiv2021

Gain control by sparse, ultra-slow glycinergic synapses

SO_SCPLOWUMMARYC_SCPLOWRetinal ON starburst amacrine cells (SACs) play a critical role in computing stimulus direction, partly in service of image stabilization by optokinetic nystagmus. ON SAC responses are sculpted by rich GABAergic innervation, mostly from neighbouring SACs. Surprisingly, however, we find that glycinergic narrow field amacrine cells (NACs) serve as their dominant source of inhibition during sustained activity. Although NAC inputs constitute only [~]5% of inhibitory synapses to ON SACs, their distinct input patterns enable them to drive glycine inhibition during the both light increments and decrements. NAC-to-ON-SAC inhibition appears to be mediated by ultra-slow non-canonical glycine receptors containing the 4 subunit, which effectively summate during repetitive stimulation. Glycinergic inhibition strongly decreases the output gain of the SACs, ensuring that their direction-selective output is maintained over their operating range. These results reveal an unexpected role for glycinergic pathways and receptor kinetics in modulating direction selectivity in the retina.

neuroscience↗

bioRxiv2020

In vivo imaging of the kinetics of microglial self-renewal and maturation in the adult visual cortex

Microglia are the resident immune cells in the brain with the capacity to autonomously self-renew. Under basal conditions, microglial self-renewal appears to be slow and stochastic, although microglia have the ability to proliferate very rapidly following depletion or in response to injury. Because microglial self-renewal has largely been studied using static tools, the mechanisms and kinetics by which microglia renew and acquire mature characteristics in the adult brain are not well understood. Using chronic in vivo two-photon imaging in awake mice and PLX5622 (Colony stimulating factor 1 receptor (CSF1R) inhibitor) to deplete microglia, we set out to understand the dynamic self-organization and maturation of microglia following depletion in the visual cortex. We confirm that under basal conditions, cortical microglia show limited turnover and migration. Following depletion, however, microglial repopulation is remarkably rapid and is sustained by the dynamic division of the remaining microglia in a manner that is largely independent of signaling through the P2Y12 receptor. Mathematical modeling of microglial division demonstrates that the observed division rates can account for the rapid repopulation observed in vivo. Additionally, newly-born microglia resemble mature microglia, in terms of their morphology, dynamics and ability to respond to injury, within days of repopulation. Our work suggests that microglia rapidly self-renew locally, without the involvement of a special progenitor cell, and that newly born microglia do not recapitulate a slow developmental maturation but instead quickly take on mature roles in the nervous system. Graphical Abstract(a) Microglial dynamics during control condition. Cartoon depiction of the heterogenous microglia in the visual cortex equally spaced. (b) During the early stages of repopulation, microglia are irregularly spaced and sparse. (c) During the later stages of repopulation, the number of microglia and the spatial distribution return to baseline. (d-f) We then created and ran a mathematical model that sampled the number of microglia, (d) the persistent doublets, (e) the rapid divisions of microglia and (f) the secondary divisions of microglia during the peak of repopulation day 2-day 3. The mathematical model suggested that residual microglia can account for the rapid repopulation we observed in vivo. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/977553v2_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@e198cborg.highwire.dtl.DTLVardef@f6484aorg.highwire.dtl.DTLVardef@1041083org.highwire.dtl.DTLVardef@1d8499a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗