Biology subjects

Wilson, L.

Publications and source records attributed to Wilson, L..

34 records · Page 2Linked to original sources

bioRxiv2023

ST3Gal1 synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer

Immune checkpoint blockade trials have yet to produce a robust anti-cancer response in prostate cancer patients as a monotherapy due to the immunosuppressed prostate cancer tumour immune microenvironment. ST3Gal1 and other sialyltransferases are implicated in cancer and immune suppression by synthesizing sialoglycans, which act as ligands for Siglec receptors. These checkpoints are important for the immune response. However, its unclear how the synthesis of Siglec ligands is regulated, and little is known about the role of sialoglycan-Siglec-axis in prostate cancers evasion of anti-tumour immunity. We report that ST3Gal1 levels negatively correlate with androgen signalling in prostate tumours. Utilising syngeneic mouse models, we demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion. Using mouse models, patient samples and in vitro models we show that ST3Gal1 synthesises sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. For the first time we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. Importantly, we show that these interactions can be modulated by enzalutamide and may maintain immune suppression in enzalutamide treated tumours. We conclude that the activity of ST3Gal1 is critical to prostate cancer anti-tumour immunity and provide rationale for the use of glyco-immune checkpoint targeting therapies in advanced prostate cancer.

cancer biology↗

bioRxiv2022

Three-dimensional imaging and single-cell transcriptomics of the human kidney implicate perturbation of lymphatics in alloimmunity

Studies of the structural and molecular features of the lymphatic vasculature, which clears fluid, macromolecules and leukocytes from the tissue microenvironment, have largely relied on animal models, with limited information in human organs beyond traditional immunohistochemical assessment. Here, we use three-dimensional imaging and single-cell RNA-sequencing to study lymphatics in the human kidney. We found a hierarchical arrangement of lymphatic vessels within human kidneys, initiating along specialised nephron epithelium in the renal cortex and displaying a distinct, kidney-specific transcriptional profile. In chronic transplant rejection we found kidney allograft lymphatic expansion alongside a loss of structural hierarchy, with human leukocyte antigen-expressing lymphatic vessels infiltrating the medulla, presenting a putative target for alloreactive antibodies. This occurred concurrently with lymphatic vessels invading and interconnecting tertiary lymphoid structures at early stages of lymphocyte colonisation. Analysis of intercellular signalling revealed upregulation of co-inhibitory molecule-mediated CD4+ T cell-lymphatic crosstalk in rejecting kidneys, potentially acting to limit local alloimmune responses. Overall, we delineate novel structural and molecular features of human kidney lymphatics and reveal perturbations to their phenotype and transcriptome in the context of alloimmunity. SUMMARYLymphatics regulate fluid balance and immune cell accumulation but are under-studied in human organs such as the kidney. Jafree and colleagues profiled human kidney lymphatics using three-dimensional imaging and single-cell RNA-sequencing, revealing structural and transcriptional perturbations in rejecting kidney transplants.

immunology↗

bioRxiv2022

Complexes of tubulin oligomers and tau form an intervening network cross-bridging microtubules into bundles

The axon-initial-segment (AIS) of mature neurons contains microtubule (MT) fascicles (linear bundles) that are implicated as retrograde diffusion barriers in the retention of MT-associated protein (MAP) tau inside axons. While the role of tau in MT bundling is poorly understood, tau dysfunction and leakage outside of the axon is associated with neurodegeneration. We report on the structure of steady-state MT bundles in response to varying concentrations of divalent cations (Mg2+ or Ca2+) in dissipative reaction mixtures containing {beta}-tubulin, full-length tau, and GTP at 37{degrees}C. A concentration-time kinetic phase diagram generated by synchrotron small-angle X-ray scattering (SAXS) reveals a wide-spacing MT bundle phase (Bws), a transient intermediate MT bundle phase (Bint), and a tubulin ring phase. Remarkably, SAXS analysis combined with TEM of plastic embedded samples provides direct evidence of an intervening network (IN) of complexes of tubulin oligomers and tau ({approx}5 nm wide filaments), which stabilize MT bundles. In this model, {beta}-tubulin oligomers in the IN are crosslinked by taus MT binding repeats, which also link {beta}-tubulin oligomers to {beta}-tubulin within the MT lattice. The finding of a new role for tubulin revises current dogma where cross-bridging of MTs is attributed entirely to interactions between MAPs. The tubulin-tau complexes of the IN should enhance the barrier properties of MT fascicles in preventing tau missorting to the somatodendritic compartment as happens during neurodegeneration. Furthermore, tubulin-tau complexes in the IN or bound to isolated MTs are potential sites for enzymatic modification of tau promoting nucleation and growth of tau fibrils in tauopathies. Significance StatementA cell free model of microtubule (MT) bundles of the axon-initial-segment (known as MT fascicles) was studied in physiologically relevant buffer conditions. MT fascicles have a role in retaining neuronal protein tau, a key protein stabilizing MTs, in the axon. X-ray scattering and electron microscopy led to the discovery of complexes of tubulin oligomers and tau as building blocks of an intervening network that cross-bridge MTs into stable bundles with precisely the same linear geometry observed in-vivo in neurons. Significantly, changes to the chemical structure of tau because of abnormal interactions with cellular enzymes, would be predicted to disrupt the intervening tubulin-tau network and the MT-fascicles barrier function, promoting leakage of tau to the somatodendritic compartment and neuron degradation.

biophysics↗

bioRxiv2022

Long-term population decline of a genetically homogenous continental-wide top Arctic predator

Genetic analysis can provide valuable information for conservation programs by unraveling the demographic trajectory of populations, by estimating effective population size, or by inferring genetic differentiation between populations. Here, we investigated the genetic differentiation within the Snowy Owl (Bubo scandiacus), a species identified as vulnerable by the IUCN, to (i) quantify connectivity among wintering areas, (ii) to evaluate current genetic diversity and effective population size and (iii) to infer changes in the historical effective population size changes from the last millennia to the recent past. The Snowy Owl, a highly mobile top predator, breeds across the Arctic tundra which is a region especially sensitive to current climate change. Using SNP-based analyses on Snowy Owls sampled across the North American nonbreeding range, we found an absence of genetic differentiation among individuals located up to 4,650 km apart. Our results suggest high genetic intermixing and effective dispersal at the continental scale despite documented philopatry to nonbreeding sites in winter. Reconstructing the population demographic indicated that North American Snowy Owls have been steadily declining since the Last Glacial Maximum ca 20,000 years ago and concurrently with global increases in temperature. Conservation programs should now consider North American Snowy Owls as a single, genetically homogenous continental-wide population which is most likely sensitive to the long-term global warming occurring since the Last Glacial Maximum.

ecology↗

bioRxiv2021

But Mouse, you are not alone: On some severe acute respiratory syndrome coronavirus 2 variants infecting mice

In silico predictions combined with in vitro, in vivo and in situ observations collectively suggest that mouse adaptation of the SARS-CoV-2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike proteins receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements due to more favourable binding interactions with residues on the complementary angiotensin-converting enzyme 2 (ACE2) interface, are however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta, Gamma, and Omicron variants of concern infecting mice, while Delta and Delta Plus lack a similar biomolecular basis to do so. This paper identifies eleven countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.

bioinformatics↗

bioRxiv2021

Optimized nickase- and nuclease-based prime editing in human and mouse cells

Precise genomic modification using prime editing (PE) holds enormous potential for research and clinical applications. Currently, the delivery of PE components to mammalian cell lines requires multiple plasmid vectors. To overcome this limitation, we generated all-in-one prime editing (PEA1) constructs that carry all the components required for PE, along with a selection marker. We tested these constructs (with selection) in HEK293T, K562, HeLa and mouse embryonic stem (ES) cells. We discovered that PE efficiency in HEK293T cells was much higher than previously observed, reaching up to 95% (mean 67%). The efficiency in K562 and HeLa cells, however, remained low. To improve PE efficiency in K562 and HeLa, we generated a nuclease prime editor and tested this system in these cell lines as well as mouse ES cells. PE-nuclease greatly increased prime editing initiation, however, installation of the intended edits was often accompanied by extra insertions derived from the repair template. Finally, we show that zygotic injection of the nuclease prime editor can generate correct modifications in mouse fetuses with up to 100% efficiency. In summary, PE-nuclease and the PEA1 plasmids provide new tools to generate intended edits with high efficiency.

molecular biology↗

bioRxiv2021

Repurposing diphenylbutylpiperidine-class antipsychotic drugs for host-directed therapy of Mycobacterium tuberculosis and Salmonella enterica infections

The persistent increase of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) infections negatively impacts Tuberculosis (TB) treatment outcomes. Host-directed therapies (HDT) pose an complementing strategy, particularly since Mtb is highly successful in evading host-defense by manipulating host-signaling pathways. Here, we screened a library containing autophagy-modulating compounds for their ability to inhibit intracellular Mtb-bacteria. Several active compounds were identified, including two drugs of the diphenylbutylpiperidine-class, Fluspirilene and Pimozide, commonly used as antipsychotics. Both molecules inhibited intracellular Mtb in pro- as well as anti-inflammatory primary human macrophages in a host-directed manner and synergized with conventional anti-bacterials. Importantly, these inhibitory effects extended to MDR-Mtb strains and the unrelated intracellular pathogen, Salmonella enterica serovar Typhimurium (Stm). Mechanistically Fluspirilene and Pimozide were shown to regulate autophagy and alter the lysosomal response, partly correlating with increased bacterial localization to autophago(lyso)somes. Pimozides and Fluspirilenes efficacy was inhibited by antioxidants, suggesting involvement of the oxidative-stress response in Mtb growth control. Furthermore, Fluspirilene and especially Pimozide counteracted Mtb-induced STAT5 phosphorylation, thereby reducing Mtb phagosome-localized CISH that promotes phagosomal acidification. In conclusion, two approved antipsychotic drugs, Pimozide and Fluspirilene, constitute highly promising and rapidly translatable candidates for HDT against Mtb and Stm and act by modulating the autophagic/lysosomal response by multiple mechanisms.

immunology↗

bioRxiv2021

Saccharide Analysis of Onion Outer Epidermal Walls

BackgroundEpidermal cell walls have special structural and biological roles in the life of the plant. Typically they are multi-ply structures encrusted with waxes and cutin which protect the plant from dehydration and pathogen attack. These characteristics may also reduce chemical and enzymatic deconstruction of the wall for sugar analysis and conversion to biofuels. We have assessed the saccharide composition of the outer epidermal wall of onion scales with different analytical methods. This wall is a particularly useful model for cell wall imaging and mechanics. ResultsEpidermal walls were depolymerized by acidic methanolysis combined with 2 M trifluoracetic acid hydrolysis and the resultant sugars were analyzed by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Total sugar yields based on wall dry weight were low (53%). Removal of waxes with chloroform increased the sugar yields to 73% and enzymatic digestion did not improve these yields. Analysis by gas chromatography/mass spectrometry (GC/MS) of per-O-trimethylsilyl (TMS) derivatives of the sugar methyl glycosides produced by acidic methanolysis gave a high yield for galacturonic acid (GalA) but glucose (Glc) was severely reduced. In a complementary fashion, GC/MS analysis of methyl alditols produced by permethylation gave substantial yields for glucose and other neutral sugars, but GalA was severely reduced. Analysis of the walls by 13C solid-state NMR confirmed and extended these results and revealed 15% lipid content after chloroform extraction (potentially cutin and unextractable waxes). ConclusionsAlthough exact values vary with the analytical method, our best estimate is that polysaccharide in the outer epidermal wall of onion scales is comprised of homogalacturonan (~50%), cellulose (~20%), galactan (~10%), xyloglucan (~10%) and smaller amounts of other polysaccharides. Low yields of specific monosaccharides by some methods may be exaggerated in epidermal walls impregnated with waxes and cutin and call for cautious interpretation of the results.

plant biology↗

bioRxiv2020

Multiple pathways of LRRK2-G2019S / Rab10 interaction in dopaminergic neurons

BackgroundInherited mutations in the LRRK2 protein are the most common known cause of Parkinsons, but the mechanisms by which increased kinase activity of mutant LRRK2 leads to pathological events remain to be determined. In vitro assays (heterologous cell culture, phospho-protein mass spectrometry) suggest that several Rab proteins might be directly phosphorylated by LRRK2-G2019S. Which Rabs interact with LRRK2 in dopaminergic neurons to facilitate normal and pathological physiological responses remains to be determined. An in vivo screen of Rab expression in dopaminergic neurons in young adult Drosophila demonstrated a strong genetic interaction between LRRK2-G2019S and Rab10. We now ask if Rab10 is required for LRRK2-induced physiological responses in DA neurons. MethodsLRRK2-G2019S was expressed in Drosophila dopaminergic neurons and the effects of Rab10 depletion on Proboscis Extension, vision, circadian activity pattern and courtship memory determined in aged flies. ResultsRab10 loss-of-function rescued bradykinesia of the Proboscis Extension Response (PER) and visual defects of aged flies expressing LRRK2-G2019S in DA neurons. Rab10 knock-down however, did not rescue the marked sleep phenotype which results from dopaminergic expression of LRRK2-G2019S. Courtship memory is not affected by LRRK2 expression, but is markedly improved by Rab10 depletion. Anatomically, both LRRK2-G2019S and Rab10 are seen in the cytoplasm and at the synaptic endings of dopaminergic neurons. ConclusionsWe conclude that, in Drosophila dopaminergic neurons, Rab10 is involved differentially in LRRK2-induced behavioral deficits. Therefore, variations in Rab expression may contribute to susceptibility of different dopaminergic nuclei to neurodegeneration seen in people with Parkinsons. Graphical AbstractRab10 depletion ameliorates the proboscis extension bradykinesia and loss of synaptic signalling in the retina induced by LRRK2-G2019S expression (magenta arrows / orange crosses). Rab10 manipulation does not affect the sleep phenotype from LRRK2-G2019S (magenta arrow). Reduction of Rab10 facilitates conditioned courtship memory, but LRRK2 has no effect (yellow arrow). All manipulations of Rab10 and G2019S in dopaminergic neurons, shown in the outline of the brain (filled cells have high levels of Rab10). We conclude that Rab10 and LRRK2 interact in some, but not all dopaminergic neurons. This may underlie differences in the susceptibility of different human striatal dopaminergic cells to Parkinsons and explain why different symptoms initiate particular ages. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/316992v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1e9a923org.highwire.dtl.DTLVardef@15f7135org.highwire.dtl.DTLVardef@101525borg.highwire.dtl.DTLVardef@1c5da02_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Cellular taxonomy and spatial organization of the ventral posterior hypothalamus reveals neuroanatomical parcellation of the mammillary bodies

The ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell types in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in a selection of neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit a surprising degree of segregation within neuroanatomical subdivisions of the MB, while genetically-defined MB cell types project topographically to the anterior thalamus. This single cell transcriptomic atlas of cell types in the VPH provides a detailed resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits in health and disease.

neuroscience↗

bioRxiv2020

Structure and mechanism of potent bifunctional β-lactam- and homoserine lactone-degrading enzymes from marine microorganisms

Genes that confer antibiotic resistance can rapidly be disseminated from one microorganism to another by mobile genetic elements, thus transferring resistance to previously susceptible bacterial strains. The misuse of antibiotics in health care and agriculture has provided a powerful evolutionary pressure to accelerate the spread of resistance genes, including those encoding {beta}-lactamases. These are enzymes that are highly efficient in inactivating most of the commonly used {beta}-lactam antibiotics. However, genes that confer antibiotic resistance are not only associated with pathogenic microorganisms, but are also found in non-pathogenic (i.e. environmental) microorganisms. Two recent examples are metal-dependent {beta}-lactamases (MBLs) from the marine organisms Novosphingobium pentaromativorans and Simiduia agarivorans. Previous studies have demonstrated that their {beta}-lactamase activity is comparable to those of well-known MBLs from pathogenic sources (e.g. NDM-1, AIM-1) but that they also possess efficient lactonase activity, an activity associated with quorum sensing. Here, we probed the structure and mechanism of these two enzymes using crystallographic, spectroscopic and fast kinetics techniques. Despite highly conserved active sites both enzymes demonstrate significant variations in their reaction mechanisms, highlighting both the extraordinary ability of MBLs to adapt to changing environmental conditions and the rather promiscuous acceptance of diverse substrates by these enzymes.

biochemistry↗

bioRxiv2019

Altered active control of step width in response to mediolateral leg perturbations while walking

During human walking, step width is predicted by mediolateral motion of the pelvis, a relationship that can be attributed to a combination of passive body dynamics and active sensorimotor control. The purpose of the present study was to investigate whether humans modulate the active control of step width in response to a novel mechanical environment. Participants were repeatedly exposed to a force-field that either assisted or perturbed the normal relationship between pelvis motion and step width, separated by washout periods to detect the presence of potential after-effects. As intended, force-field assistance directly strengthened the relationship between pelvis displacement and step width. This relationship remained strengthened with repeated exposure to assistance, and returned to baseline afterward, providing minimal evidence for assistance-driven changes in active control. In contrast, force-field perturbations directly weakened the relationship between pelvis motion and step width. Repeated exposure to perturbations diminished this negative direct effect, and produced larger positive after-effects once the perturbations ceased. Both of these results provide evidence of gradual changes in active control in response to perturbations. In the longer term, these methods may be useful for improving deficits in the active control of step width often observed among clinical populations with poor walking balance.

bioengineering↗

bioRxiv2019

Broad spectrum antibiotic-degrading metallo-β-lactamases are phylogenetically diverse and widespread in the environment.

Antibiotic resistance has emerged as a major global health threat. The Zn2+-dependent metallo-{beta}-lactamases (MBLs) are of particular concern as they act on the most widely prescribed class of antibiotics, the {beta}-lactams, and are largely unaffected by commonly used {beta}-lactamase antagonists such as clavulanic acid. MBLs are subdivided into three groups (B1 to B3); despite low overall sequence similarity, their catalytic centers are conserved with two closely spaced Zn2+ binding sites ( and {beta} site). We recovered almost 1500 B3 MBLs from >100,000 public microbial genomes representing a wide range of habitats including pristine sites not impacted by human activity. Although homologs were predominantly identified in members of the bacterial phylum Proteobacteria, the recovered B3 MBLs represent a much broader phylogenetic diversity than is currently appreciated based on the study of model pathogens. This includes three active site variants inferred to have arisen from the ancestral B3 enzyme. One of these variants, B3-RQK, is noteworthy for being broadly sensitive to clavulanic acid. Through targeted mutations we demonstrate that the presence of a lysine residue (Lys263) in the {beta} site of the catalytic center of this variant confers sensitivity to this compound. Replacing this lysine with the canonical histidine (His263) found in all other MBLs restored resistance. Crystallographic and computational data reveal that clavulanic acid inhibits B3-RQK MBLs by displacing the Zn2+ ion in the {beta} site. Therefore, modifying clavulanic acid to effectively interact with His263 may increase the therapeutic range of this widely used antibiotic resistance drug.\n\nSignificanceThis study surveys the environmental and phylogenetic diversity of the B3 subgroup of antibiotic-degrading metallo-{beta}-lactamases (MBLs). B3-like MBLs are more widespread in the environment than previously appreciated suggesting multiple unrecognized reservoirs of antibiotic resistance. Three variants of the canonical active site were identified, including B3-RQK, which amongst the B3 MBLs is uniquely inhibited by the antibiotic resistance drug clavulanic acid. We demonstrate that the mode of inhibition involves the displacement of a catalytically essential Zn2+ ion from the active site. It may thus be possible to modify clavulanic acid so that it can compete with the Zn2+ ions in other MBLs as well, increasing the therapeutic range of this compound.

biochemistry↗

bioRxiv2019

High-throughput propagation of human prostate tissue from induced-pluripotent stem cells

Primary culture of human prostate organoids is slow, inefficient and laborious. To overcome this, we demonstrate a new high-throughput model where rapidly proliferating and easily handled induced pluripotent stem cells, for the first time, enable generation of human prostate tissue in vivo and in vitro. Using a co-culture technique with urogenital sinus mesenchyme, we recapitulated the in situ prostate histology, including the stromal compartment and the full spectrum of epithelial differentiation. This approach overcomes major limitations in primary cultures of human prostate stem, luminal and neuroendocrine cells, as well as the stromal microenvironment. These models provide new opportunities to study prostate development, homeostasis and disease.

developmental biology↗

bioRxiv2019

Neurodegeneration caused by LRRK2-G2019S requires Rab10 in select dopaminergic neurons

Inherited mutations in the LRRK2 protein are the commonest known cause of Parkinsons, but the molecular link from increased kinase activity to pathological neurodegeneration remains to be determined. In vitro (biochemical and cell culture) assays led to the hypothesis that several Rab GTPases might be LRRK2 substrates. Here we show that Rab10 potently modifies LRRK2-G2019S mediated electrophysiological responses in an in vivo screen, in which each Rab was overexpressed in Drosophila dopaminergic neurons. We therefore tested the effect of Rab10 loss of function on three LRRK2-G2019S phenotypes (vision, movement and sleep) that rely on dopaminergic circuits in both flies and mammals. The knock-out of Rab10 in vivo fully rescues the reduced responses induced by dopaminergic LRRK2-G2019S in visual and motor (reaching, proboscis extension) assays, but the sleep phenotype is unaffected. We show that Rab10 is expressed in dopaminergic (tyrosine hydroxylase positive) neurons controlling vision and proboscis movement, but undetectable in those controlling sleep, indicating that anatomical and physiological patterns of Rab10 are related. Our results support the idea that LRRK2 phosphorylates separate targets in distinct neurons and confirm that one degenerative pathway starts with Rab10. Although Rab3 is another putative substrate of LRRK2, it shows no synergy with G2019S and localises to a different subset of dopaminergic neurons from Rab10. We propose that variations in Rab expression may contribute to differences in the rate of neurodegeneration seen in different dopaminergic nuclei in Parkinsons.\n\nSignificance StatementA key question in Parkinsons is why dopamine neurons die particularly fast in some parts of the substantia nigra. We focused on the commonest Parkinsons-related mutation, LRRK2-G2019S. In vitro assays suggested that neurodegeneration may start by LRRK2-G2019S increasing phosphorylation of Rab10. We found Rab10 in fly dopamine neurons in visual and motor pathways, but not in the sleep system. Rab10 knock-out rescues G2019S-induced visual and movement degeneration, leaving sleep dysfunction unaffected. Thus, LRRK2 activates at least two pathways, one Rab10-dependent, leading to neurodegeneration in vivo. Rab3 is found in a different subset of dopaminergic neurons and shows no synergy with LRRK2-G2019S. We propose that variations in Rab expression contribute to differences in neurodegeneration seen in Parkinsons.

neuroscience↗

bioRxiv2018

Detection of a novel insect specific flavivirus across ecologically diverse populations of Aedes aegypti on the Caribbean Island of Saint Lucia

Outbreaks of mosquito-borne arboviral diseases including dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV) and chikungunya virus (CHIKV) have recently occurred in the Caribbean. The geographical range of the principle vectors responsible for transmission, Aedes (Ae.) aegypti and Ae. albopictus is increasing and greater mosquito surveillance is needed in the Caribbean given international tourism is so prominent. The island of Saint Lucia has seen outbreaks of DENV and CHIKV in the past five years but vector surveillance has been limited with the last studies dating back to the late 1970s. Natural disasters have changed the landscape of Saint Lucia and the island has gone through significant urbanisation. In this study, we conducted an entomological survey of Ae. aegypti and Ae. albopictus distribution across the island and analysed environmental parameters associated with the presence of these species. Although we collected Ae. aegypti across a range of sites across the island, no Ae. albopictus were collected despite traps being placed in diverse ecological settings. The number of Ae. aegypti collected was significantly associated with higher elevation and semi-urban settings yielded female mosquito counts per trap-day that were 5-fold lower than urban settings. Screening for arboviruses revealed a high prevalence of a novel insect-specific flavivirus closely related to cell fusing agent virus (CFAV). We discuss the implications that natural disasters, water storage and lack of mosquito surveillance have on arboviral outbreaks in Saint Lucia and implications for insect only flaviviruses on surveillance and detection of pathogenic flaviviruses.

ecology↗