Biology subjects

Johnson, A. F.

Publications and source records attributed to Johnson, A. F..

6 recordsLinked to original sources

bioRxiv2024

The global fish and invertebrate abundance value of mangroves

Mangroves are a critical coastal habitat that provides a suite of ecosystem services and supports livelihoods. We undertake the first global analysis to estimate density and abundance of 37 commercially important fish and invertebrates that are known to extensively use mangroves. Geomorphic mangrove type, sea surface salinity and temperature, and length of mangrove forest edge were important in predicting the density of commercial fish and invertebrates, with deltaic systems supporting the highest densities. The model predicted high densities throughout parts of southeast Asia, the northern coast of South America, the Red Sea, and the Caribbean and Central America. Application of our model onto the global mangrove extent, estimates that mangroves support the annual abundance of nearly 800 billion young-of-year fish and invertebrates contained in our model. Our results confirm the critical role of mangroves globally in supporting fish and fisheries, and further builds the case for their conservation and restoration.

ecology↗

bioRxiv2022

KaryoCreate: a new CRISPR-based technology to generate chromosome-specific aneuploidy by targeting human centromeres

Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer and congenital syndromes. Here, we describe KaryoCreate (Karyotype CRISPR Engineered Aneuploidy Technology), a system that enables generation of chromosome-specific aneuploidies by co-expression of a sgRNA targeting chromosome-specific CENPA-binding [a]-satellite repeats together with dCas9 fused to a mutant form of KNL1. We designed unique and highly specific sgRNAs for 19 out of 24 chromosomes. Expression of these sgRNAs with KNL1Mut-dCas9 leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny with an average efficiency of 8% and 12% for gains and losses, respectively (up to 20%), tested and validated across 9 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, a frequent occurrence in gastrointestinal cancers, promotes resistance to TGF{beta}, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe a novel technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond. HighlightsO_LIWe designed sgRNAs targeting chromosome-specific centromeres across 19 human chromosomes C_LIO_LIKaryoCreate combines chromosome-specific centromeric sgRNAs with dCas9 fused to a mutant form of KNL1. C_LIO_LIKaryoCreate allows engineering gains and losses of specific human chromosomes. C_LIO_LIEngineered Chromosome 18q loss promotes tumor-associated phenotypes in colon-derived cells. C_LIO_LIKaryoCreate is a CRISPR-based technology to foster the study of centromere biology and aneuploidy. C_LI

cell biology↗

bioRxiv2022

Towards transboundary networks of climate-smart marine reserves in the Southern California Bight

Climate-smart conservation addresses the vulnerability of biodiversity to climate change impacts but may require transboundary considerations. Here, we adapt and refine 16 biophysical guidelines for climate-smart marine reserves for the transboundary California Bight ecoregion. We link several climate-adaptation strategies (e.g., maintaining connectivity, representing climate refugia, and forecasting effectiveness of protection) by focusing on kelp forests and associated species. We quantify transboundary larval connectivity along [~]800 km of coast and find that the number of connections and the average density of larvae dispersing through the network under future climate scenarios could decrease by [~]50%, highlighting the need to protect critical steppingstone nodes. We also find that although focal species will generally recover with 30% protection, marine heatwaves could hinder subsequent recovery in the following 50 years, suggesting that protecting climate refugia and expanding the coverage of marine reserves is a priority. Together, these findings provide a first comprehensive framework for integrating climate resilience for networks of marine reserves and highlight the need for a coordinated approach in the California Bight ecoregion.

ecology↗

bioRxiv2021

Pro-IL-18 secreted by keratinocytes detects the group A streptococcal protease SpeB

Group A Streptococcus (GAS, Streptococcus pyogenes) is a professional human pathogen that commonly infects the skin. Keratinocytes are one of the first cells to contact GAS, and by inducing inflammation, they can initiate the earliest immune responses to pathogen invasion. Here, we characterized the proinflammatory cytokine repertoire produced by primary human keratinocytes and surrogate cell lines commonly used in vitro. Infection induces several cytokines and chemokines, but keratinocytes constitutively secrete IL-18 in a form that is inert (pro-IL-18) and lacks proinflammatory activity. Canonically, IL-18 activation and secretion are coupled through a single proteolytic event that is regulated intracellularly by the inflammasome protease caspase-1 in myeloid cells. The pool of extracellular pro-IL-18 generated by keratinocytes is poised to sense extracellular proteases and is directly processed into a mature active form by SpeB, a secreted GAS protease that is a critical virulent factor during skin infection. This mechanism contributes to the proinflammatory response against GAS, resulting in T cell activation and the secretion of IFN-{gamma} that restrict GAS growth. Other major bacterial pathogens and microbiota of this skin did not have significant IL-18-maturing ability. Taken together, these results suggest keratinocyte-secreted IL-18 is a sentinel that sounds an early alarm that is highly sensitive to GAS, yet tolerant to non-invasive members of the microbiota.

microbiology↗

bioRxiv2020

Factors contributing to the disease ecology of brown crab (Cancer pagurus) in a temperate marine protected area.

Marine ecosystems are affected by multiple, well-known stressors like fishing and climate change, but a less documented concern is disease. Marine reserves have been successful in replenishing stocks and aiding recruitment but studies have shown that high population abundances in marine reserves may lead to unwanted secondary effects such as increase in predators and competition, altering trophic webs, and disease. Here, we investigate factors contributing to disease prevalence in a brown crab (Cancer pagurus) population around Lundy Island (the UKs first MPA) after 7 years of no-take protection. Population parameters (size, sex, and abundance), disease (shell disease, Hematodinium spp. infection) and injury presence (a known precursor to some disease conditions) were assessed over two years in both fished and unfished areas of the MPA. We found no significant difference in prevalence between the disease prevalence in fished and unfished areas, however overall, the number of injured crabs increased significantly over the two years (12%), as did the prevalence of shell disease (15%). The probability of crabs having shell disease increased significantly in male crabs, and in those missing limbs. The probability of crabs being injured increased significantly in crabs below the minimum landing size. In terms of population parameters, crabs were more prevalent in the fished area compared to the unfished area, thought to be a result of an increase in the predatory European lobster. The findings of the present study highlight potential secondary community changes as a result of MPA implementation. Therefore, surveillance for such changes, as part of MPA management, would provide useful information on the health and overall function of the protected ecosystem.

ecology↗

bioRxiv2020

Group A Streptococcus Infection of the Nasopharynx Requires Proinflammatory Signaling Through the Interleukin-1 Receptor

Group A Streptococcus (GAS) is the etiologic agent of numerous high morbidity and high mortality diseases which commonly have a highly proinflammatory pathology. One factor contributing to this inflammation is the GAS protease SpeB, which directly activates the proinflammatory cytokine interleukin-1{beta} (IL-1{beta}), independent of the canonical inflammasome pathway. IL-1{beta} drives neutrophil activation and recruitment that limits bacterial growth and invasion during invasive skin and soft tissue infections like necrotizing fasciitis. GAS also causes pharyngitis (strep throat), and the upper respiratory tract is its primary nidus for growth and transmission. Since the fitness selection for the species is likely primarily for this site, we examined the process of IL-1{beta} activation in the murine nasopharynx. SpeB still activated IL-1{beta}, which was required for neutrophil migration, but this inflammation instead increased GAS replication. Inhibiting IL-1{beta} or depleting neutrophils, which both promote invasive infection, prevented GAS infection of the nasopharynx. Prior antibiotic exposure increased GAS growth in the murine nasopharynx, and antibiotics were sufficient to reverse the attenuation previously observed when IL-1{beta}, neutrophils, or SpeB were not present to drive inflammation. Therefore, the same fundamental mechanism has opposing effects on virulence at different body sites. Invasive disease may be limited in part due to specific adaptations for inducing host inflammation that are beneficial for pharyngitis. IMPORTANCEOur previous reports showed that Group A Streptococcus (GAS) protease SpeB directly activates the host proinflammatory cytokine IL-1{beta} and this restricts invasive skin infection. The upper respiratory tract is the primary site of GAS colonization and infection, but the host-pathogen interactions at this site are still largely unknown. We provide the first evidence that IL-1{beta}-mediated inflammation promotes upper respiratory tract infection. This provides experimental evidence that the notable inflammation of strep throat, which presents with significant swelling, pain, and neutrophil influx, is not an ineffectual immune response, but rather is a GAS-directed remodeling of this niche for its pathogenic benefit.

microbiology↗