Biology subjects

Harvey, G.

Publications and source records attributed to Harvey, G..

6 recordsLinked to original sources

bioRxiv2026

The Two Tube Volatile Assay: a non-contact benchtop bioassay for monitoring susceptibility to transfluthrin

IntroductionProgress against malaria has stalled since 2015, with insecticide resistance a key driver. Spatial emanators release volatile insecticides into the air, exposing mosquitoes through a route distinct from the tarsal contact used by treated nets, indoor residual spraying, and standard bioassays. Transfluthrin is currently monitored using the WHO bottle bioassay, which combines contact and vapour exposure and cannot isolate airborne effects. A scalable, vapour-only method is needed to characterise susceptibility to volatile pyrethroids. MethodsWe adapted the WHO tube bioassay to deliver non-contact transfluthrin vapour exposure without contacting treated papers. Non-blood-fed female Anopheles were exposed to acetone control or transfluthrin papers at 0.005, 0.1 and 2 mg/paper. Knockdown was recorded over 60 minutes and mortality at 24 hours. Testing spanned three laboratories (LSTM, AIRID and KEMRI) using susceptible reference and resistant lab colonies. Dose response models estimated EC{square}{square} for knockdown (EC{square}{square}KD) and mortality (EC{square}{square}Mort), with resistance ratios (RR) against the local susceptible reference. ResultsThe assay generated clear concentration- and time-dependent responses. At LSTM, Kisumu gave an EC{square}{square}KD of 0.052 and EC{square}{square}Mort of 0.054 mg/paper; Siaya was comparable (RR{square}{square}KD 1.17, RR{square}{square}Mort 0.89), whereas Tiassale 13 and KDR showed reduced susceptibility (RR{square}{square}KD 2.42 and 2.85; RR{square}{square}Mort 5.56 and 6.65). At AIRID, the resistant Cove strain did not reach 50% knockdown or mortality. At KEMRI, Siaya showed reduced susceptibility (RR{square}{square}KD 3.36/RR{square}{square}Mort 5.65). Kisumu at AIRID and KEMRI was comparable to LSTM (EC{square}{square}KD 0.007/EC{square}{square}Mort 0.030; EC{square}{square}KD 0.044/EC{square}{square}Mort 0.023). Despite inter-laboratory variation, susceptible strains remained distinguishable from resistant ones. Lower RRs than for contact pyrethroids suggest contact-based phenotypes may not predict vapour susceptibility. ConclusionThe assay provides a practical benchtop method using standard WHO hardware, distinguishing susceptible from resistant strains across three laboratories. Twenty-four-hour mortality is the recommended endpoint, 60-minute knockdown secondary. Not yet validated, it provides a foundation for further validation and adaptation to other actives.

zoology↗

bioRxiv2026

Multi-centre laboratory study to determine discriminating concentrations for broflanilide and isocycloseram resistance monitoring in mosquitoes

1In 2024-2025 a multi-centre study involving seven international laboratories was conducted with the support of the World Health Organization (WHO). The aim of the study was to establish and validate discriminating concentrations (DCs) in WHO bottle bioassays for monitoring susceptibility to broflanilide and isocycloseram in Anopheles gambiae s.s., An. funestus, An. stephensi and Aedes aegypti. The following values are recommended for adoption as DCs for broflanilide: 10 {micro}g/bottle for An. gambiae and Ae. aegypti, 15 {micro}g/bottle for An. funestus, and 25 {micro}g/bottle for An. stephensi. The recommended DCs for isocycloseram are 15 {micro}g/bottle for Ae. aegypti, 30 {micro}g/bottle for An. gambiae, 50 {micro}g/bottle for An. stephensi, and 60 {micro}g/bottle for An. funestus. Based on the experiences of conducting this study, which represents the application of a generic protocol for establishing discriminating concentrations produced by the WHO, technical recommendations are made on the generation and analysis of DC data for insecticides in future.

zoology↗

bioRxiv2026

Serpin-Driven Green Camouflage and NIR Fluorescence in Frogs

Animals have evolved multiple strategies to generate optical traits and coloration. While most amphibians rely on a three-dimensional arrangement of chromatophores in the skin, hundreds of arboreal frog species achieve leaf-like green color through a different mechanism involving reduced pigmentation, subcutaneous biological mirrors, and high concentrations of the blood-derived pigment biliverdin. Although biliverdin is rapidly excreted in most vertebrates, hylid and centrolenid frogs can retain it through the binding to a serpin-family protein (BBS). Here we show that BBSs bind biliverdin with high affinity (Kd < 10 nM), comparable to hormone-receptor interactions. This interaction alters biliverdins spectral signature in ways that resemble those of green-leaf pigments. BBSs from different species exhibit distinct biophysical properties, accounting for interspecific differences in color saturation and hue. Unlike most serpins in vivo, BBS of the glassfrog Teratohyla pulverata is naturally cleaved, yielding a highly thermostable, thermodynamically favored protein, without loss of affinity. Using custom-designed hyperspectral photoacoustic tomography (PAT), we demonstrate that BBS is widely distributed throughout the body, contributing to whole-body color and camouflage. Furthermore, we show that BBSs emit near-infrared (NIR) fluorescence (>700 nm) rendering these frogs fluorescent in a spectral region where biological tissues are largely transparent. Together, BBSs shed light on serpin evolution, protein thermostability, amphibian color diversity, and the development of NIR molecular probes.

biochemistry↗

bioRxiv2022

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

BackgroundCanine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells associated with short survival times. Understanding the genomic landscape of HSA is critical to developing more effective therapeutic strategies. ObjectivesTo determine the relationships between genomic and clinical features including treatment and outcome in canine splenic HSA. Animals109 dogs with primary splenic HSA treated by splenectomy that had tumor sequencing via the FidoCure(R) Precision Medicine Platform targeted sequencing panel. MethodsPatient signalment, weight, metastasis at diagnosis, treatment, and survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables and outcome were assessed. ResultsSomatic mutations in TP53 (n = 45), NRAS (n = 20), and PIK3CA (n = 19) were most common. Survival was associated with metastases at diagnosis, germline variants in SETD2 and NOTCH1, and nominally with breed. Age at diagnosis was associated with NRAS mutations and breed. TP53 and PIK3CA mutations were found in larger dogs, germline SETD2 variants in smaller dogs. Doxorubicin (DOX) treatment did not significantly improve survival time, while targeted therapies had a significant early survival benefit. Conclusions and clinical importanceDOX treatment may provide limited clinical benefit for dogs with splenic HSA, while targeted therapy may provide early survival benefit. Genetic signatures associated with splenic HSA may be useful in guiding targeted therapy to improve outcomes. Germline variants, age, size, and breed may be useful prognostic factors and provide insight into the genomic landscape of the tumor.

genomics↗

bioRxiv2021

Shared hotspot mutations in spontaneously arising cancers position dog as an unparalleled comparative model for precision therapeutics

Naturally occurring canine cancers have remarkable similarities to their human counterparts. In order to determine whether these similarities occur at the molecular level, we investigated hotspot mutations in a variety of spontaneously arising canine cancers and found high concordance in oncogenic drivers between cancers in both species. These findings suggest that canines may present a powerful and complementary model for preclinical investigations for targeted cancer therapeutics. Through analysis of 708 client-owned dogs from 96 breeds (plus mixed breeds) with 23 common tumor types, we discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. TP53 is the most commonly mutated gene, detected in 30.81% of canine tumors overall and >40% in hemangiosarcoma and osteosarcoma. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant (P<0.0001) association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E in urothelial carcinoma. This work positions canines as excellent spontaneous models of human cancers that can help to investigate a wide spectrum of targeted therapies.

cancer biology↗

bioRxiv2020

Disruption of a GATA2, TAL1, ERG regulatory circuit promotes erythroid transition in healthy and leukemic stem cells

Changes in gene regulation and expression govern orderly transitions from hematopoietic stem cells to terminally differentiated blood cell types. These transitions are disrupted during leukemic transformation but knowledge of the gene regulatory changes underpinning this process is elusive. We hypothesised that identifying core gene regulatory networks in healthy hematopoietic and leukemic cells could provide insights into network alterations that perturb cell state transitions. A heptad of transcription factors (LYL1, TAL1, LMO2, FLI1, ERG, GATA2, RUNX1) bind key hematopoietic genes in human CD34+ haematopoietic stem and progenitor cells (HSPCs) and have prognostic significance in acute myeloid leukemia (AML). These factors also form a densely interconnected circuit by binding combinatorially at their own, and each others, regulatory elements. However, their mutual regulation during normal haematopoiesis and in AML cells, and how perturbation of their expression levels influences cell fate decisions remains unclear. Here, we integrated bulk and single cell data and found that the fully connected heptad circuit identified in healthy HSPCs persists with only minor alterations in AML, and that chromatin accessibility at key heptad regulatory elements was predictive of cell identity in both healthy progenitors and in leukemic cells. The heptad factors GATA2, TAL1 and ERG formed an integrated sub-circuit that regulates stem cell to erythroid transition in both healthy and leukemic cells. Components of this triad could be manipulated to facilitate erythroid transition providing a proof of concept that such regulatory circuits could be harnessed to promote specific cell type transitions and overcome dysregulated haematopoiesis.

cancer biology↗