Biology subjects

Anthony, S.

Publications and source records attributed to Anthony, S..

7 recordsLinked to original sources

bioRxiv2026

Multi-site phenotypic characterisation of Kisumu colonies for comparison of insecticide susceptibility between testing centres

Testing of insecticides and insecticide-based vector control tools relies on the use of bioassays whereby insects are exposed and mortality, or another relevant entomological endpoint, is measured. To be able to compare results between products and across time and space standard laboratory strains are used. Insecticide-susceptible strains are often used as comparators in studies involving insecticide-resistant populations. Kisumu is a long-established, widely-used insecticide-susceptible strain of Anopheles gambiae. In this study, 16 facilities across different countries exposed their Kisumu colonies aged 3-5 days to four insecticides (permethrin, alpha-cypermethrin, DDT and pirimiphos-methyl) at a range of concentrations in WHO tube assays to assess susceptibility. Insecticide-treated filter papers were made at the Liverpool School of Tropical Medicine and sent to testing centres, along with a standard protocol and testing conditions requirements, to standardise testing as much as possible. A first observation was that DDT results were affected by the use of Risella oil, the WHO-recommended carrier oil but immiscible in acetone, leading to uneven coating of papers and increased variability in bioassay results (40x variance between colonies). Bioassay data generated by the testing facilities suggest a wide range of susceptibility to different insecticides between colonies of Kisumu: LC50 values between colonies differed, though not significantly, by up to 4x for permethrin, 6x for pirimiphos-methyl, and 15x for alpha-cypermethrin. Some colonies are classified as insecticide resistant based on the WHO definition of <98% mortality on exposure to a discriminating concentration. The assumption that Kisumu is a standard susceptible strain, consistent between facilities is challenged, which has implications when comparing results between studies. We propose genotypic analysis of the colonies to identify signs of resistance markers indicative of contamination from resistant strains or wild mosquitoes, and generation of guidance to support the maintenance and monitoring of susceptible mosquito strains.

zoology↗

bioRxiv2026

Comparison of Four Assays That Measure Antibodies to Ebola Virus Glycoprotein

The accurate measurement of Ebola virus (EBOV)-specific antibody responses is crucial to assessing immunity induced by EBOV infection or vaccination. For this purpose, the Filovirus Animal Nonclinical Group (FANG) anti-EBOV glycoprotein (GP1,2) ELISA is considered the "gold-standard". However, it has limitations such as high repeat-rates and variability, and low throughput. Here, we describe two new alternative assays: a Single-Molecule Assay Planar EBOV GP1,2 ELISA and a multiplexed EBOV GP1,2, EBOV nucleoprotein, and EBOV Viral Protein 40 Luminex assay, and compare these with two versions of the FANG ELISA. Samples were selected from participants receiving vaccine or placebo in a randomized, placebo-controlled, double-blinded study of two EBOV vaccines (PREVAIL 1), and a longitudinal cohort study of Ebola virus disease (EVD) survivors and their close contacts (PREVAIL 3). All four assays were concordant in their measurements of anti-EBOV GP1,2-specific immunoglobulin G responses, allowing for the determination of conversion equations for antibody measurements across assays. In addition, all four showed a similar ability to distinguish vaccine recipients from placebo recipients and EVD survivors from their close contacts. Compared to the FANG assays, the Quanterix and Luminex assays had lower variability, lower repeat rates, and higher throughput, making them good alternatives for future studies.

immunology↗

bioRxiv2025

Direct interoceptive input to the insular cortex shapes learned feeding behavior

The insular cortex (insula) is an interoceptive hub, which senses internal states such as hunger, thirst, pain, and emotions. Previous studies suggest that the insula directly senses internal states, but the mechanisms remain elusive. We identified a population of leptin receptor-positive cells with a unique morphology in the insula (INSLepR). Based on leptins known role in signaling adiposity, we hypothesized that INSLepR neurons detect internal states to regulate food intake and body weight. Accordingly, we found that intra-insula leptin administration or optogenetic stimulation of INSLepR neurons impacts feeding behavior. Moreover, INSLepR neuron activity encodes feeding bouts in an internal-state dependent manner, and leptin alters insula neural dynamics in response to feeding, while also reshaping the transcriptome. Taken together, our data supports a model for direct interoceptive input to the insula, in which INSLepR cells integrate adiposity level signals to regulate feeding and body weight in a learned manner.

neuroscience↗

bioRxiv2023

Evolutionary potential of the monkeypox genome arising from interactions with human APOBEC3 enzymes

APOBEC3, an enzyme subfamily that plays a role in virus restriction by generating mutations at particular DNA motifs or mutational "hotspots," can drive viral mutagenesis with host-specific preferential hotspot mutations contributing to pathogen variation. While previous analysis of viral genomes from the 2022 Mpox (formerly Monkeypox) disease outbreak has shown a high frequency of C>T mutations at TC motifs, suggesting recent mutations are human APOBEC3-mediated, how emerging monkeypox virus (MPXV) strains will evolve as a consequence of APOBEC3-mediated mutations remains unknown. By measuring hotspot under-representation, depletion at synonymous sites, and a combination of the two, we analyzed APOBEC3-driven evolution in human poxvirus genomes, finding varying hotspot under-representation patterns. While the native poxvirus molluscum contagiosum exhibits a signature consistent with extensive coevolution with human APOBEC3, including depletion of TC hotspots, variola virus shows an intermediate effect consistent with ongoing evolution at the time of eradication. MPXV, likely the result of recent zoonosis, showed many genes with more TC hotspots than expected by chance (over-representation) and fewer GC hotspots than expected (under-representation). These results suggest the MPXV genome: 1) may have evolved in a host with a particular APOBEC GC hotspot preference, 2) has inverted terminal repeat (ITR) regions -which may be exposed to APOBEC3 for longer during viral replication- and longer genes likely to evolve faster, and therefore 3) has a heightened potential for future human APOBEC3-meditated evolution as the virus spreads in the human population. Our predictions of MPXV mutational potential can both help guide future vaccine development and identification of putative drug targets and add urgency to the task of containing human Mpox disease transmission and uncovering the ecology of the virus in its reservoir host.

bioinformatics↗

bioRxiv2018

To: Plos OneKnowledge, experiences and perceptions of the Ghana National Health Insurance Scheme in three districts

BackgroundGhanas National Health Insurance Scheme is a demand side programme where the governing authority registers clients and purchases health care services for them from public and private providers. Access of services is high across a broad Benefits Package with no parallel enrolment necessary for any type of service at the point of access. Nonetheless, there is evidence of difficulty in acquiring and use of the NHIS card to access health care services.\n\nObjectiveWhile studies had been conducted into general awareness, there was no linkage between awareness, uptake and experiences with registration and use of the card. This study fills this gap.\n\nMethodsThis is a descriptive study. A mix of qualitative (39 Focus Group Discussions) and quantitative (625 household interviews) methods were used to collect the data. Qualitative data was analysed manually using a thematic approach while a frequency analysis was done for the quantitative data.\n\nResultsKnowledge about the Scheme was near universal. Enrolment was lower among FGD discussants, 38.7% had valid cards, than for household respondents, 62.9% valid cards. While mixed experiences with the registration process was observed among FGD discussants, 74% of the households ranked attitudes of Scheme staff as positive. The study found the NHIS card facilitates access to facility based health care. Satisfaction levels with use of the card were mixed and contextual among discussants. However, 90% of households reported their cards were readily accepted at health facilities. Expired card (51.4%) and health facility had stopped accepting NHIS cards (14.3%) were mentioned as reasons for non-acceptance.\n\nConclusionPeoples experience during registration and use of the NHIS card to access health care has lasting effect on their perceptions of the Scheme. This can be harnessed to manage the high expectations, grow membership, discourage frivolous use and address artificial barriers of access.

scientific communication and education↗

bioRxiv2018

Antibody-based vaccine for TB: pre-clinical validation in horse foals challenged with the TB-related pathogen Rhodococcus equi

Immune correlates for protection against Mycobacterium tuberculosis (Mtb) infection and other intracellular pathogens are largely undetermined. Whether there is a role for antibody-mediated immunity is controversial. Rhodococcus equi is an intracellular pathogen causing severe pneumonia in young horse foals, eliciting a disease with many similarities to TB including intracellular residence, formation of granulomas and induction of severe respiratory distress. No purified vaccine antigens exist for R. equi or Mtb infections. Both express the microbial surface polysaccharide antigen poly-N-acetyl glucosamine (PNAG). Vaccination of pregnant mares with a synthetic PNAG oligosaccharide conjugated to tetanus toxoid elicited antibody that transferred to foals via colostrum and provided nearly complete protection against R. equi pneumonia in a randomized, controlled, blinded challenge trial. Infusion of PNAG-hyperimmune plasma protected 100% of foals against R. equi pneumonia. Vaccination induced opsonic antibodies that killed extracellular and intracellular R. equi and other intracellular pathogens. Killing of intracellular organisms was dependent on antibody recognition of surface expression of PNAG on infected macrophages, complement deposition and PMN-assisted lysis of infected macrophages. Protection also correlated with PBMC release of interferon-{gamma} in response to PNAG. Antibody-mediated opsonic killing and interferon-{gamma} release in response to PNAG may protect against disease caused by intracellular bacterial pathogens.

immunology↗

bioRxiv2017

IMPDH polymers accommodate both catalytically active and inactive conformations

Several metabolic enzymes undergo reversible polymerization into macromolecular assemblies. The function of these assemblies is often unclear but in some cases they regulate enzyme activity and metabolic homeostasis. The guanine nucleotide biosynthetic enzyme inosine monophosphate dehydrogenase (IMPDH) forms octamers that polymerize into helical chains. In mammalian cells, IMPDH filaments can associate into micron-length assemblies. Polymerization and enzyme activity are regulated in part by binding of purine nucleotides to an allosteric regulatory domain. ATP promotes octamer polymerization, whereas GTP promotes a compact, inactive conformation whose ability to polymerize is unknown. An open question is whether polymerization directly alters IMPDH catalytic activity. To address this, we identified point mutants of human IMPDH2 that either prevent or promote polymerization. Unexpectedly, we found that polymerized and non-assembled forms of IMPDH have comparable catalytic activity, substrate affinity, and GTP sensitivity and validated this finding in cells. Electron microscopy revealed that substrates and allosteric nucleotides shift the equilibrium between active and inactive conformations in both the octamer and the filament. Unlike other metabolic filaments, which selectively stabilize active or inactive conformations, IMPDH filaments accommodate multiple states. Thus, although polymerization alone does not impact catalytic activity, substrate availability and purine balance dramatically affect IMPDH filament architecture.

biochemistry↗