Biology subjects

Johnson, J. S.

Publications and source records attributed to Johnson, J. S..

18 recordsLinked to original sources

bioRxiv2026

Gut archaea drive human MAIT cell responses

Archaea, the third domain of life, are a gut microbiome constituent, but their role in shaping immunity is poorly understood. Mucosal-associated invariant T (MAIT) cells sense microbial metabolites through their T cell receptor and contribute to antimicrobial defence and barrier homeostasis. Key sources of the major MAIT cell antigen 5-OP-RU within the human gut microbiome are unknown. Analysing microbiomes from UK, Zambian, Kenyan and Ugandan donors, we found strong correlations between archaeal riboflavin biosynthesis and circulating MAIT cell frequency and activation. Stool 5-OP-RU levels correlated with archaeal abundance. Cultures of methanogenic archaea, including the human commensal Methanobrevibacter smithii, produced 5-OP-RU and strongly activated MAIT cells without inflammation. We demonstrate a critical role for archaea in shaping human immunity, with implications for microbiome-mediated regulation of health.

immunology↗

bioRxiv2026

The impact of Cronartium ribicola inoculum density on quantitative disease resistance in whitebark pine.

Whitebark pine (Pinus albicaulis), a wide-ranging high-elevation conifer in western North America, is listed as threatened in the U.S. and as endangered in Canada. A major threat to whitebark pine is the non-native, invasive white pine blister rust disease, caused by the fungal pathogen Cronartium ribicola. In many pathosystems (including white pine blister rust), seedling inoculation trials are used to identify parent trees with genetic resistance. However, many of these trials use only one spore density for inoculation, and little information exists on the effectiveness of quantitative disease resistance (QDR) under varying spore densities and the corresponding implications for field performance. In this study, we examine the levels of infection and survival present within six whitebark pine seedling families previously rated for QDR (three susceptible and three resistant families) under six widely varying inoculum densities. The susceptible families showed very high infection and mortality at all inoculum densities, while performance of the resistant families varied with spore density treatment. The information gathered from the study will be useful in updating the projections of the future of whitebark pine populations under field conditions in areas of different rust hazard. The results also serve as a caution to those working in other pathosystems where seedling inoculation trials based on one spore density level are used to rate the resistance level of parent trees and their associated progeny.

genetics↗

bioRxiv2025

Spatial Attention Weakly Modulates Visual Responses in the Lateral Geniculate Nucleus

Visual responses in the cerebral cortex are strongly influenced by shifts in spatial attention. This modulation of visual processing includes changes in firing rate, decreased response variability, and decreased interneuronal correlations; all of which are thought to underlie enhanced visual perception near the center of attention at the cost of visual perception at other locations. Visual information from the retina is relayed to primary visual cortex via neurons in the lateral geniculate nucleus (LGN) of the dorsal thalamus. Although early studies describe an enhancement of LGN activity with spatial attention, more recent work has cast doubt on this view. Given its strategic position as the gateway to the cortex, an understanding of the effects of attention on visual processing in the LGN is important. We therefore performed experiments to reexamine the influence of covert spatial attention on the spiking activity of single units in the macaque LGN and applied a broad set of analyses and functional metrics to assess possible effects. Our results reveal a statistically significant effect of spatial attention in the LGN: firing rates were slightly higher and more reliable when monkeys directed attention towards the receptive fields of recorded neurons compared to when attention was directed to different retinotopic locations. However, effects were much smaller than previously reported ([~]1% vs [~]4%) and further analyses suggest that effects are weak and inconsistent. Thus, while spatial attention does exert an influence in the LGN, its effects are weak and may have limited impact on downstream processing. Significance StatementThe lateral geniculate nucleus (LGN) is a critical relay in the visual system, shaping the flow of sensory information from the eye to the brain. Although higher-order brain regions show strong modulation by attention, it remains unclear whether the LGN is similarly affected. By directly recording LGN activity in monkeys performing a covert attention task, we found that spatial attention produces only weak and inconsistent modulation of visual responses. These findings suggest that the LGN largely operates independently of spatial attention, highlighting a potential boundary between early sensory processing and cognitive control.

neuroscience↗

bioRxiv2024

Hierarchical emergence of opponent coding in auditory belt cortex

We recorded from neurons in primary auditory cortex (A1) and middle-lateral belt area (ML) while rhesus macaques either discriminated amplitude-modulated noise (AM) from unmodulated noise or passively heard the same stimuli. We used several post-hoc pooling models to investigate the ability of auditory cortex to leverage population coding for AM detection. We find that pooled-response AM detection is better in the active condition than the passive condition, and better using rate-based coding than synchrony-based coding. Neurons can be segregated into two classes based on whether they increase (INC) or decrease (DEC) their firing rate in response to increasing modulation depth. In these samples, A1 had relatively fewer DEC neurons (26%) than ML (45%). When responses were pooled without segregating these classes, AM detection using rate-based coding was much better in A1 than in ML, but when pooling only INC neurons, AM detection in ML approached that found in A1. Pooling only DEC neurons resulted in impaired AM detection in both areas. To investigate the role of DEC neurons, we devised two pooling methods that opposed DEC and INC neurons - a direct subtractive method and a two-pool push-pull opponent method. Only the push-pull opponent method resulted in superior AM detection relative to indiscriminate pooling. In the active condition, the opponent method was superior to pooling only INC neurons during the late portion of the response in ML. These results suggest that the increasing prevalence of the DEC response type in ML can be leveraged by appropriate methods to improve AM detection.

neuroscience↗

bioRxiv2024

Dynamic Human Gut Microbiome and Immune Shifts During an Immersive Psychosocial Therapeutic Program

BackgroundDepression is a leading cause of disability worldwide yet its underlying factors, particularly microbial associations, are poorly understood. MethodsWe examined the longitudinal interplay between the microbiome and immune system in the context of depression during an immersive psychosocial intervention. 142 multi-omics samples were collected from 52 well-characterized participants before, during, and three months after a nine-day inquiry-based stress reduction program. ResultsWe found that depression was associated with both an increased presence of putatively pathogenic bacteria and reduced microbial beta-diversity. Following the intervention, we observed reductions in neuroinflammatory cytokines and improvements in several mental health indicators. Interestingly, participants with a Prevotella-dominant microbiome showed milder symptoms when depressed, along with a more resilient microbiome and more favorable inflammatory cytokine profile, including reduced levels of CXCL-1. ConclusionsOur findings reveal a protective link between the Prevotella-dominant microbiome and depression, associated with a less inflammatory environment and moderated symptoms. These insights, coupled with observed improvements in neuroinflammatory markers and mental health from the intervention, highlight potential avenues for microbiome-targeted therapies in depression management.

microbiology↗

bioRxiv2024

Cell-free reconstitution of HIV-1 innate immune sensing reveals the capsid is a molecular cloak that protects reverse transcripts from cGAS

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect viral genomes from cGAS even after completing reverse transcription. Viral DNA could be "deprotected" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, the capsid inhibitor lenacapavir also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling.

microbiology↗

bioRxiv2021

Laterally transferred macrophage mitochondria acts as a signaling source promoting cancer cell proliferation

Lateral transfer of mitochondria occurs in many physiological and pathological conditions. Given that mitochondria provide essential energy for cellular activities, mitochondrial transfer is currently thought to promote the rescue of damaged cells. We report that mitochondrial transfer occurs between macrophages and breast cancer cells, leading to increased cancer cell proliferation. Unexpectedly, transferred macrophage mitochondria are dysfunctional, lacking mitochondrial membrane potential. Rather than performing essential mitochondrial activities, transferred mitochondria accumulate reactive oxygen species which activates ERK signaling, indicating that transferred mitochondria act as a signaling source that promotes cancer cell proliferation. We also demonstrate that pro-tumorigenic M2-like macrophages exhibit increased mitochondrial transfer to cancer cells. Collectively, our findings reveal how mitochondrial transfer is regulated and leads to sustained functional changes in recipient cells. One-Sentence SummaryLateral transfer of macrophage mitochondria acts as a ROS signaling source, regulating cancer cell proliferation through ERK signaling.

cancer biology↗

bioRxiv2021

Acetylated Chromatin Domains Link Chromosomal Organization to Cell- and Circuit-level Dysfunction in Schizophrenia and Bipolar Disorder

To explore modular organization of chromosomes in schizophrenia (SCZ) and bipolar disorder (BD), we applied population-scale correlational structuring of 739 histone H3-lysine 27 acetylation and H3-lysine 4 trimethylation profiles, generated from the prefrontal cortex (PFC) of 568 cases and controls. Neuronal histone acetylomes and methylomes assembled as thousands of cis-regulatory domains (CRDs), revealing fine-grained, kilo-to megabase scale chromatin organization at higher resolution but firmly integrated into Hi-C chromosomal conformations. Large clusters of domains that were hyperacetylated in disease shared spatial positioning within the nucleus, predominantly regulating PFC projection neuron function and excitatory neurotransmission. Hypoacetylated domains were linked to inhibitory interneuron- and myelination-relevant genes. Chromosomal modular architecture is affected in SCZ and BD, with hyperacetylated domains showing unexpectedly strong convergences defined by cell type, nuclear topography, genetic risk, and active chromatin state across a wide developmental window.

genomics↗

bioRxiv2020

Ten-year projection of white-nose syndrome disease dynamics at the southern leading-edge of infection in North America

Predicting the emergence and spread of infectious diseases is critical for effective conservation of biodiversity. White-nose syndrome (WNS), an emerging infectious disease of bats, has resulted in high mortality in eastern North America. Because the fungal causative agent Pseudogymnoascus destructans is constrained by temperature and humidity, spread dynamics may vary greatly by geography. Environmental conditions in the southern part of the continent, where disease dynamics are typically studied, making it difficult to predict how the disease will manifest. Herein, we modeled the spread of WNS in Texas based on available cave densities and average dispersal distances of species occupying these sites, and projected these results out to 10 years. We parameterized a predictive model of WNS epidemiology and its effects on hibernatory bat populations with observed environmental data from bat hibernation sites in Texas. Our model suggests that bat populations in northern Texas will be more affected by WNS mortality than southern Texas. As such, we recommend prioritizing the preservation of large overwintering colonies of bats in north Texas through management actions. Our model further illustrates that infectious disease spread and infectious disease severity can become uncoupled over a gradient of environmental variation. Finally, our results highlight the importance of understanding host, pathogen and environmental conditions in various settings to elucidate what may happen across a breadth of environments.

ecology↗

bioRxiv2020

Winter activity of boreal bats

Natural hibernation sites used by bats in areas that lack cave features have long remained unresolved. To investigate hibernation site selection and winter activity of boreal bats, we recorded bat calls using passive acoustic monitoring on 16 sites. These sites included four rock outcrops with crevices and cave features, three glacial erratics or boulder fields, three ancient shores, three root cellars and three control sites where we did not expect bats to be overwintering. Our results revealed echolocation calls of Eptesicus nilssonii, Plecotus auritus and Myotis sp. We recorded significantly more activity near rock outcrops and root cellars compared to other habitats. We also found that ambient temperature had a positive effect on bat activity and found evidence that P. auritus may be using low barometric pressure as a proxy for suitable foraging conditions during the winter. Our results suggest that rock outcrops may be more important to bats than previously acknowledged, highlighting the need to take these sites in account in planning of conservation measures. Furthermore, our findings underline the suitability of using acoustic monitoring in homing on hibernation sites that are not otherwise accessible.

zoology↗

bioRxiv2020

A Genome-wide CRISPR-Cas9 Screen Identifies Host Factors Essential for Optimal Plasmodium Liver Stage Development.

Prior to initiating symptomatic malaria, a single Plasmodium sporozoite infects a hepatocyte and develops into thousands of merozoites, in part by scavenging host resources. We show that host microtubules dynamically reorganize around the developing liver stage (LS) parasite. Using a genome-wide CRISPR-Cas9 screen, we identified host regulators of cytoskeleton organization, vesicle trafficking, ER/Golgi stress and lipid biogenesis that regulate Plasmodium LS development. These novel regulators of infection, including Centromere Protein J (CENPJ), led us to interrogate how microtubule organizing centers (MTOCs) are regulated during infection. Foci of {gamma}-tubulin localized to the parasite periphery; depletion of CENPJ exacerbated this re-localization and increased infection. Further, we show that the Golgi acts as a non-centrosomal MTOC by organizing {gamma}-tubulin and stimulating microtubule nucleation at the parasite periphery. Collectively, we show that the Plasmodium LS recruits the host Golgi to form MT mediated conduits along which host organelles are recruited to the PVM, to support liver stage development. Our findings suggest many host-targeted pharmacological inhibitors may inhibit LS infection.

cell biology↗

bioRxiv2020

Roosting ecology of the southernmost bats, Myotis chiloensis and Histiotus magellanicus, in southern Tierra del Fuego, Chile

There are few studies of day-roosting ecology of bats inhabiting the southernmost forests of South America, where cool summer temperatures and land management practices pose several challenges. The goal of the present study was to describe day-roosting habitats and patterns of thermoregulation in two bat species occurring on Tierra del Fuego, Myotis chiloensis (Chilean myotis) and Histiotus magellanicus (southern big-eared brown bat), during late spring. To do so, we tagged 17 bats with temperature-sensitive radio-transmitters, located 17 day-roosts, and collected 81 days of skin temperature data. We concurrently recorded ambient air temperature to determine its effect on torpor use. Both species were found roosting in large diameter (77.8 {+/-} 6 cm), typically live, Nothofagus pumilio trees (lenga) located on the edges of forest gaps or within stands primarily composed of smaller, younger trees. Bats of both species frequently used torpor, with skin temperatures dropping below a torpor threshold on 89% of days (n = 72) and daily minimum skin temperatures averaging 16.5 {degrees}C over the course of our study. Average daily air temperature was a significant predictor of torpor use, with lower skin temperatures and more time spent in torpor observed on colder days. Minimum skin temperature and time spent torpid did not vary between bat species, nor did the characteristics of day-roosts. These data show that spring temperatures in Tierra del Fuego pose an energetic challenge that bats meet through frequent use of torpor, and likely, habitat selection. We recommend local conservation efforts keep these thermal challenges in mind by retaining large trees, which may provide warmer microclimates or room for social groups.

ecology↗

bioRxiv2020

Population connectivity predicts vulnerability to white-nose syndrome in the Chilean myotis (Myotis chiloensis) - a genomics approach

Despite its peculiar distribution, the biology of the southernmost bat species in the world, the Chilean myotis (Myotis chiloensis), has garnered little attention so far. The species has a north-south distribution of c. 2800 km, mostly on the eastern side of the Andes mountain range. Use of extended torpor occurs in the southernmost portion of the range, putting the species at risk of bat white-nose syndrome (WNS), a fungal disease responsible for massive population declines in North American bats. Here, we examined how geographic distance and topology would be reflected in the population structure of M. chiloensis along the majority of its range using a double digestion RAD-tag method. We sampled 66 individuals across the species range and discovered pronounced isolation-by-distance. Furthermore, and surprisingly, we found higher degrees of heterozygosity in the southernmost populations compared to the north. A coalescence analysis revealed that our populations may still not have reached secondary contact after the Last Glacial Maximum. As for the potential spread of pathogens, such as the fungus causing WNS, connectivity among populations was noticeably low, especially between the southern hibernatory populations in the Magallanes and Tierra del Fuego, and more northerly populations. This suggests the probability of geographic spread of the disease from the north through bat-to-bat contact to susceptible populations is low. The study presents a rare case of defined population structure in a bat species and warrants further research on the underlying factors contributing to this.

evolutionary biology↗

bioRxiv2020

Hierarchical effects of choice related activity and neural encoding during feature selective attention

Selective attention is necessary to sift through, form a coherent percept of, and make behavioral decisions on the vast amount of information present in most sensory environments. How and where selective attention is employed in cortex and how this perceptual information then informs the relevant behavioral decisions is still not well understood. Studies probing selective attention and decision making in visual cortex have been enlightening as to how sensory attention might work in that modality; whether or not similar mechanisms are employed in auditory attention is not yet clear. Therefore, we trained rhesus macaques on a feature selective attention task, where they switched between reporting changes in temporal (amplitude modulation, AM) and spectral (carrier bandwidth) features of a broadband noise stimulus. We investigated how the encoding of these features by single neurons in primary (A1) and secondary (lateral belt, ML) auditory cortex were affected by the different attention conditions. We found that neurons in A1 and ML showed mixed-selectivity to the sound and task features. We found no difference in AM encoding between the attention conditions. We found that choice-related activity in both A1 and ML neurons shifts between attentional conditions. This finding suggests that choice-related activity in auditory cortex does not simply reflect motor preparation or action, and supports the relationship between reported choice-related activity and the decision and perceptual process. New & NoteworthyWe recorded from primary and secondary auditory cortex while monkeys performed a non-spatial feature attention task. Both areas exhibited rate-based choice-related activity. The manifestation of choice-related activity was attention-dependent, suggesting that choice-related activity in auditory cortex does not simply reflect arousal or motor influences, but relates to the specific perceptual choice. The lack of temporal-based choice activity is consistent with growing evidence that subcortical, but not cortical, single neurons inform decisions through temporal envelope following.

neuroscience↗

bioRxiv2020

Amplitude modulation encoding in auditory cortex: Comparisons between the primary and middle lateral belt regions

In macaques, the middle lateral auditory cortex (ML) is a belt region adjacent to primary auditory cortex (A1) and believed to be at a hierarchically higher level. Although ML single-unit responses have been studied for several auditory stimuli, the ability of ML cells to encode amplitude modulation (AM) - an ability which has been widely studied in A1 - has not yet been characterized. Here we compare the responses of A1 and ML neurons to amplitude modulated (AM) noise in awake macaques. While several of the basic properties of A1 and ML responses to AM noise are similar, we found several key differences. ML neurons do not phase lock as strongly, are less likely to phase lock, and are more likely to respond in a non-synchronized fashion than A1 cells, consistent with a temporal-to-rate transformation as information ascends the auditory hierarchy. ML neurons tend to have lower temporally (phase-locking) based best modulation frequencies than A1. At the level of ML, neurons that decrease firing rate with increasing modulation depth become more common than in A1. In both A1 and ML we find a prevalent class of neurons with excitatory rate responses at lower modulation frequencies and suppressed rate responses relative to the unmodulated carrier at middle modulation frequencies.

neuroscience↗

bioRxiv2019

SVants: A long-read based method for structural variation detection in bacterial genomes

MotivationMobile genetic elements (MGEs) are genetic material that can transfer between bacterial cells and move to new locations within a single bacterial genome. These elements range from several hundred to tens of thousands of bases, and are often bordered by repeat regions, which makes resolving these elements difficult with short-read sequencing data. The development and availability of long-read sequencing technologies has opened up new opportunities in the study of structural variation but there is a lack of bioinformatics tools designed to take advantage of these longer reads.\n\nResultsWe present an assembly-free method for identifying the location of these MGEs when compared to any reference genome (including draft genomes). Using an artificially constructed Escherichia coli genome containing single and tandem-repeats of a Tn9 transposon, we demonstrate the ability of SVants to accurately identify multiple insertion sites as well as count the number of repeats of this MGE. Additionally, we show that SVants accurately identifies the transposon of interest, Tn9, but does not erroneously identify existing IS1 regions present within the chromosome of the E. coli artificial reference.\n\nAvailability and ImplementationSVants is available as open-source software at https://github.com/EpiBlake/SVants

bioinformatics↗

bioRxiv2019

A comprehensive map of the dendritic cell transcriptional network engaged upon innate sensing of HIV

Transcriptional programming of the innate immune response is pivotal for host protection. However, the transcriptional mechanisms that link pathogen sensing with innate activation remain poorly understood. During infection with HIV-1, human dendritic cells (DCs) can detect the virus through an innate sensing pathway leading to antiviral interferon and DC maturation. Here, we developed an iterative experimental and computational approach to map the innate response circuitry during HIV-1 infection. By integrating genome-wide chromatin accessibility with expression kinetics, we inferred a gene regulatory network that links 542 transcription factors with 21,862 target genes. We observed that an interferon response is required, yet insufficient to drive DC maturation, and identified PRDM1 and RARA as essential regulators of the interferon response and DC maturation, respectively. Our work provides a resource for interrogation of regulators of HIV replication and innate immunity, highlighting complexity and cooperativity in the regulatory circuit controlling the DC response to infection.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/579920_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (60K):\norg.highwire.dtl.DTLVardef@f57059org.highwire.dtl.DTLVardef@1a2f811org.highwire.dtl.DTLVardef@4c2908org.highwire.dtl.DTLVardef@19e1e9_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2018

Ferroptosis-like signaling facilitates a potent innate defense against Plasmodium infection

The facets of host control during Plasmodium liver infection remain largely unknown and conventional innate regulatory pathways are only minimally effective at eliminating parasites1-3. Ferroptosis, a recently described form of iron-dependent cell death that drives accumulation of reactive oxygen species and lipid peroxides, but has not yet been shown to function as an innate immune response4,5. Inducing ferroptosis with pharmacologicals or by genetic perturbation of its negative regulators, GPX4 and SLC7a11, dramatically reduces survival of the Plasmodium Liver Stage. In contrast, knockdown or knockout of NOX1 or knockdown of TFR1, which are required for ferroptosis, increases the number of Liver Stage parasites. Moreover, we demonstrate that blocking ferroptosis renders parasite-infected hepatocytes resistant to P53-mediated hepatocyte death. Our work establishes that ferroptotic signaling serves to control Plasmodium infection in the liver and raises the possibility that ferroptosis operates as an axis of the innate immune system to defend against intracellular pathogens.

microbiology↗