Biology subjects

Smith, R. C.

Publications and source records attributed to Smith, R. C..

27 records · Page 2Linked to original sources

bioRxiv2021

A tiger in the Upper Midwest: Surveillance and genetic data support the introduction and establishment of Aedes albopictus in Iowa, USA

Aedes albopictus is a competent vector of several arboviruses that has spread throughout the United States over the last three decades after it was initially detected in Texas in 1985. With the emergence of Zika virus in the Americas in 2015-2016 and an increased need to better understand the current distributions of Ae. albopictus in the US, we initiated surveillance efforts to determine the abundance of invasive Aedes species in Iowa. Here, we describe the resulting surveillance efforts from 2016-2020 in which we detect stable and persistent populations of Aedes albopictus in three Iowa counties. Based on temporal patterns in abundance and genetic analysis of mitochondrial DNA haplotypes between years, our data support that populations of Ae. albopictus are overwintering and have likely become established in the state. In addition, the localization of Ae. albopictus predominantly in areas of urbanization and noticeable absence in rural areas suggests that these ecological factors may represent potential barriers to their further spread and contribute to overwintering success. Together, these data document the establishment of Ae. albopictus in Iowa and their expansion into the Upper Midwest, where freezing winter temperatures were previously believed to limit their spread. With increasing globalization, urbanization, and rising temperatures associated with global warming, the range of invasive arthropod vectors, such as Ae. albopictus, is expected to only further expand, creating increased risks for vector-borne disease.

ecology↗

bioRxiv2021

Methylomic alteration in peripheral blood lymphocytes of prodromal stage and first-episode Chinese Han schizophrenia patients

BackgroundAlthough epigenetic dysregulation has long been proposed to promote the onset of schizophrenia, the landscape of the methylomic changes across the whole genome is yet established. MethodsUsing Infinium Human Methylation 850 BeadChip Array and MethylTarget sequencing method, we investigated the genome-wide methylation profiles and further validated methylation profiles of target genes in peripheral blood lymphocytes between individuals with psychosis risk syndrome (PRS), patients with first-episode schizophrenia (FES) and healthy controls (HC) in Chinese Han population. ResultsWe detected 372 sites between psychosis risk syndrome (PRS) and healthy controls (HC), which increased to 460 sites in first-episode schizophrenia (FES) with 207 sites shared. Both PRS and FES featured profound hypomethylation within gene body. Gene ontology and network annotation merged on loci enriched in disease associated signaling pathways (MAPK(Mitogen Activated Protein Kinases), Glutamatergic, GABAergic etc.). ConclusionsOur study implicated characteristic hypomethylation in both the discovery and validation cohorts in SYNGAP1, one of the frequently studied genes in neurodevelopmental disorders. This is the first methylome-wide association study between PRS and FES in Chinese Han population. Our findings provide potential biomarkers that can be used for future development of disease therapy and management.

genetics↗

bioRxiv2020

Identification of a prostaglandin E2 receptor that regulates mosquito oenocytoid immune cell function in limiting bacteria and parasite infection

Lipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet studies have been limited by the absence of a described prostaglandin receptor. Here, we characterize a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and examine its contributions to innate immunity. AgPGE2R expression is most abundant in circulating hemocytes where it is primarily localized to oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing by RNAi, we demonstrate that PGE2 signaling regulates the expression of a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs). PGE2 priming via the AgPGE2R significantly limited bacterial replication and suppressed Plasmodium oocyst survival. Additional experiments establish that PGE2 priming increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, which significantly influence Plasmodium oocyst survival. We also provide evidence that PGE2 priming is concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of PGE2 priming on anti-Plasmodium immunity. Taken together, our results characterize the AgPGE2R and the role of prostaglandin signaling on immune cell function, providing new insights into the role of PGE2 on anti-bacterial and anti-Plasmodium immune responses in the mosquito host.

immunology↗

bioRxiv2020

The 20-hydroxyecdysone agonist, halofenozide, primes anti-Plasmodium immunity in Anopheles gambiae via the ecdysone receptor

Mosquito physiology and immunity are integral determinants of malaria vector competence. This includes the principal role of hormonal signaling in Anopheles gambiae initiated shortly after blood-feeding, which stimulates immune induction and promotes vitellogenesis through the function of 20-hydroxyecdysone (20E). Previous studies demonstrated that manipulating 20E signaling through the direct injection of 20E or the application of a 20E agonist can significantly impact Plasmodium infection outcomes, reducing oocyst numbers and the potential for malaria transmission. In support of these findings, we demonstrate that a 20E agonist, halofenozide, is able to induce anti-Plasmodium immune responses that limit Plasmodium ookinetes. We demonstrate that halofenozide requires the function of ultraspiracle (USP), a component of the canonical heterodimeric ecdysone receptor, to induce malaria parasite killing responses. Additional experiments suggest that the effects of halofenozide treatment are temporal, such that its application only limits malaria parasites when applied prior to infection. Unlike 20E, halofenozide does not influence cellular immune function or AMP production. Together, our results further demonstrate the potential of targeting 20E signaling pathways to reduce malaria parasite infection in the mosquito vector and provide new insight into the mechanisms of halofenozide-mediated immune activation that differ from 20E.

microbiology↗

bioRxiv2019

Mapping biology from mouse to man using transfer learning

Biomedical research often involves conducting experiments on model organisms in the anticipation that the biology learnt from these experiments will transfer to the human. Yet, it is commonly the case that biology does not transfer effectively, often for unknown reasons. Despite its importance to translational research this transfer process is not currently rigorously quantified. Here, we show that transfer learning - the branch of machine learning that concerns passing information from one domain to another - can be used to efficiently map biology from mouse to man, using the bone marrow (BM) as a representative example of a complex tissue. We first trained an artificial neural network (ANN) to accurately recognize various different cell types in mouse BM using data obtained from single-cell RNA-sequencing (scRNA-Seq) experiments. We found that this ANN, trained exclusively on mouse data, was able to identify individual human cells obtained from comparable scRNA-Seq experiments of human BM with 83% overall accuracy. However, while some human cell types were easily identified, others were not, indicating important differences in biology. To obtain a more accurate map of the human BM we then retrained the mouse ANN using scRNA-Seq data from a limited sample of human BM cells. Typically, less than 10 human cells of a given type were needed to accurately learn its representation in the updated model. In some cases, human cell identities could be inferred directly from the mouse ANN without retraining, via a process of biologically-guided zero-shot learning. These results show how machine learning can be used to reconstruct complex biology from limited data and have broad implications for biomedical research.

systems biology↗

bioRxiv2019

20-hydroxyecdysone (20E) primes innate immune responses that limit bacteria and malaria parasite survival in Anopheles gambiae

Blood-feeding is an integral behavior of mosquitoes to acquire nutritional resources needed for reproduction. This requirement also enables mosquitoes to serve as efficient vectors to acquire and potentially transmit a multitude of mosquito-borne diseases, most notably malaria. Recent studies suggest that mosquito immunity is stimulated following a blood meal, independent of infection status. Since blood-feeding results in the increased production of the hormone 20-hydroxyecdysone (20E), we hypothesized that 20E may play an important role in priming the immune response for pathogen challenge. Herein, we examine the immunological effects of priming in Anopheles gambiae with 20E prior to pathogen infection, demonstrating a significant reduction in bacteria and Plasmodium berghei survival in the mosquito host. RNA-seq analysis following 20E treatment identifies several known 20E-regulated genes, as well as several immune genes with previously reported function in anti-pathogen defense. This includes the anti-microbial peptide cecropin 3, which we demonstrate its role as an antagonist of bacteria and Plasmodium in Anopheles gambiae and provide support that these responses are under temporal regulation. Together, these data demonstrate that 20E influences cellular immune function and anti-pathogen immunity following mosquito blood-feeding, arguing the importance of hormones in the regulation of mosquito innate immune function.

immunology↗

bioRxiv2019

Malaria parasite immune evasion and adaptation to its mosquito host is influenced by the acquisition of multiple blood meals

A minimum of two blood meals are required for a mosquito to acquire and transmit malaria, yet Anopheles mosquitoes frequently obtain additional blood meals during their adult lifespan. To determine the impact of subsequent blood-feeding on parasite development in Anopheles gambiae, we examined rodent and human Plasmodium parasite infection with or without an additional non-infected blood meal. We find that an additional blood meal significantly reduces P. berghei immature oocyst numbers, yet does not influence mature oocysts that have already begun sporogony. This is in contrast to experiments performed with the human parasite, P. falciparum, where an additional blood meal does not affect oocyst numbers. These observations are reproduced when mosquitoes were similarly challenged with an artificial protein meal, suggesting that parasite losses are due to the physical distension of the mosquito midgut. We provide evidence that feeding compromises the integrity of the midgut basal lamina, enabling the recognition and lysis of immature P. berghei oocysts by the mosquito complement system. Moreover, we demonstrate that additional feeding promotes P. falciparum oocyst growth, suggesting that human malaria parasites exploit host resources provided with blood-feeding to accelerate their growth. This contrasts experiments with P. berghei, where the size of surviving oocysts is independent of an additional blood meal. Together, these data demonstrate differences in the ability of Plasmodium species to evade immune detection and adapt to utilize host resources at the oocyst stage, representing an additional, yet unexplored component of vectorial capacity that has important implications for transmission of malaria.

microbiology↗

bioRxiv2018

Long-term surveillance defines spatial and temporal patterns implicating Culex tarsalis as the primary vector of West Nile virus in Iowa, USA

West Nile virus (WNV) has become the most epidemiologically important mosquito-borne disease in the United States, causing [~]50,000 cases since its introduction in 1999. Transmitted primarily by Culex species, WNV transmission requires the complex interplay between bird reservoirs and mosquito vectors, with human cases the result of epizootic spillover. To better understand the intrinsic factors that drive these interactions, we have compiled infection data from sentinel chickens, mosquito vectors, and human cases in Iowa over a 15 year period (2002-2016) to better understand the spatial and temporal components that drive WNV transmission. Supplementing these findings with mosquito abundance, distribution, and host preferences data, we provide strong support that Culex tarsalis is the most important vector of human WNV infections in the region. Finally, we identify underlying climatic factors (temperature and drought) that are associated with inter-annual trends in WNV intensity. Together, our analysis provides new insights into WNV infection patterns in multiple hosts and highlights the importance of long-term surveillance to understand the dynamics of mosquito-borne-disease transmission.

epidemiology↗

bioRxiv2018

Chemical depletion of phagocytic immune cells reveals dual roles of mosquito hemocytes in Anopheles gambiae anti-Plasmodium immunity

Mosquito innate immunity is comprised of both cellular and humoral factors that provide protection from invading pathogens. Immune cells, known as hemocytes, have been intricately associated with these immune responses through direct roles in phagocytosis and immune signaling. Recent studies have implicated hemocytes as integral determinants of anti-Plasmodium immunity, yet little is known regarding the specific mechanisms by which hemocytes limit malaria parasite survival. With limited genetic tools to enable their study, we employed a chemical-based treatment widely used for macrophage depletion in mammalian systems for the first time in an invertebrate organism. Upon its application in Anopheles gambiae, we observe distinct populations of phagocytic immune cells that are significantly depleted, causing high mortality following bacterial challenge and an increased intensity of malaria parasite infection. Through these studies, we demonstrate that phagocytes are required for mosquito complement recognition of invading ookinetes, as well as the production of prophenoloxidases that limit oocyst survival. Through these experiments, we also define specific sub-types of phagocytic immune cells in An. gambiae, providing new insights beyond the morphological characteristics that traditionally define mosquito hemocyte populations. Together, this study provides the first definitive insights into the dual roles of mosquito phagocytes in limiting malaria parasite survival, and illustrates the use of clodronate liposomes as an important advancement in the study of invertebrate immunity.

immunology↗