Biology subjects

Spiro, S.

Publications and source records attributed to Spiro, S..

8 recordsLinked to original sources

bioRxiv2026

Repeated and widespread introduction of a mosquito-borne virus, but wildlife impact remains localised in urban area

Mosquito-borne viruses are emerging in new regions with increasing regularity. Shifting climatic envelopes, especially in temperate regions, and altered enzootic cycles are changing likelihoods of persistence, meaning new approaches are required to predict and monitor establishment. Usutu virus (USUV) is a mosquito-borne viral zoonosis, which was first recorded in the United Kingdom in wild birds and mosquitoes in 2020. By developing a multidisciplinary approach, incorporating enhanced passive and active surveillance of wild birds, we discovered previously unrecorded introductions and identified USUV persistence and geographic expansion. By combining molecular and serological testing with citizen science derived datasets, we show an associated marked decline in a common, widespread, and highly susceptible host species (Eurasian Blackbird, Turdus merula). However, the clearest continuous signal of host population decline remains localised to a large urban area, despite the much wider virus distribution. This may be a consequence of an urban heat island effect and associated increase in length of the mosquito active season. Our results indicate that the establishment and impact of future mosquito-borne pathogens in temperate zones, anticipated under climate change, may first be most apparent in urban areas. Consequently, enhanced surveillance efforts in urban areas could provide an efficient mechanism for detecting novel pathogen emergence. The epidemiology of emerging vector-borne diseases, especially in temperate areas, depends on the interplay between climate, land-use and available hosts; therefore, considering each in isolation will not be sufficient to reliably inform surveillance or response planning.

ecology↗

bioRxiv2024

Transovarial transmission in field caught mosquitoes identifies a mechanism for the establishment of Usutu virus in a temperate country

Usutu virus (USUV) is an emerging zoonotic flavivirus in Europe, and the first zoonotic mosquito-borne virus to be confirmed in animal hosts in the United Kingdom (UK). Phylogenetic analysis of USUV in the three years following its initial detection in 2020 indicated that the virus is overwintering in the UK. In 2023, USUV was identified outside Greater London for the first time. Therefore, USUV should now be considered endemic within southeast England. Surveillance of avian hosts and mosquito vectors has been insufficient to elucidate the mechanism by which USUV has persisted through temperate winters. It is likely that mosquitoes play a significant role in facilitating the establishment of USUV in temperate areas, as is the case for related mosquito-borne viruses. Here we undertake enhanced targeted vector surveillance at the index site to investigate the role of mosquitoes in facilitating USUV establishment in the UK. Between 2021 and 2024 inclusive, we detected USUV in host-seeking adult female Culex pipiens s.l. (n = 8/554 pools), a key vector of the virus in Europe. During 2023, enhanced surveillance detected transovarial transmission of USUV in wild Cx. pipiens s.l. (n = 1/202 pools), by screening adults following captive rearing of mosquito larvae collected from the field. This is, to our knowledge, the first description of vertical transmission of USUV in an arthropod vector. Consequently, transovarial transmission should be considered a viable mechanism for the persistence of USUV in temperate areas. Our results highlight the importance of undertaking detailed vector surveillance, across life stages, to inform the epidemiology of vector-borne viruses.

microbiology↗

bioRxiv2024

Comparative neuroimaging of the carnivoran brain: Neocortical sulcal anatomy

Carnivorans are an important study object for comparative neuroscience, as they exhibit a wide range of behaviours, ecological adaptations, and social structures. Previous studies have mainly examined relative brain size, but a comprehensive understanding of brain diversity requires the investigation of other aspects of their neuroanatomy. Here, we obtained primarily post-mortem brain scans from twenty-six species of the order Carnivora, spanning across eight families with diverse representatives and including additional individuals for selected species, to create the largest Carnivoran brain collection to date. We then reconstructed their cortical surfaces, and examined neocortical sulcal anatomy to establish a framework for systematic inter-species comparisons. We observed distinct regional variations in sulcal anatomy, potentially related to the species behaviour and ecology. Arctoidea species with pronounced forepaw dexterity exhibited complex sulcal configurations in the presumed somatosensory cortex but low sulcal complexity in the presumed visual and auditory occipitotemporal cortex. Canidae had the largest number of unique major sulci with a unique sulcus in the occipital cortex and highly social canids featuring an additional frontal cortex sulcus. We also observed differentially complex occipito-temporal sulcal patterns in Felidae and Canidae, indicative of changes in auditory and visual areas that may be related to foraging strategies and social behaviour. In conclusion, this study presents an inventory of the sulcal anatomy of a number of rarely studied carnivoran brains including detailed digital atlases and establishes a framework and novel avenues for further investigations employing a variety of neuroimaging modalities to reveal more about carnivoran brain diversity.

neuroscience↗

bioRxiv2023

Choline degradation in Paracoccus denitrificans: identification of sources of formaldehyde

Paracoccus denitrificans is a facultative methylotroph that can grow on methanol and methylamine as sole sources of carbon and energy. Both are oxidized to formaldehyde and then to formate, so growth on C1 substrates induces the expression of genes encoding enzymes required for the oxidation of formaldehyde and formate. This induction involves a histidine kinase response regulator pair (FlhSR) that is likely triggered by formaldehyde. Catabolism of some complex organic substrates (for example choline and L-proline betaine) also generates formaldehyde. Thus, flhS and flhR mutants that fail to induce expression of the formaldehyde catabolic enzymes cannot grow on methanol, methylamine and choline. Choline is oxidized to glycine via glycine betaine, dimethylglycine and sarcosine. By exploring flhSR growth phenotypes and the activities of a promoter and enzyme known to be up-regulated by formaldehyde, we identify the oxidative demethylations of glycine betaine, dimethylglycine and sarcosine as sources of formaldehyde. Growth on glycine betaine, dimethylglycine and sarcosine is accompanied by the production of up to three, two and one equivalents of formaldehyde, respectively. Genetic evidence implicates two orthologous monooxygenases in the oxidation of glycine betaine. Interestingly, one of these appears to be a bifunctional enzyme that also oxidizes L-proline betaine (stachydrine). We present preliminary evidence to suggest that growth on L-proline betaine induces expression of a formaldehyde dehydrogenase distinct from the enzyme induced during growth on other formaldehyde-generating substrates. IMPORTANCEThe bacterial degradation of one carbon compounds (methanol and methylamine) and of some complex multi-carbon compounds (for example, choline) generates formaldehyde. Formaldehyde is toxic and must be removed, which can be done by oxidation to formate and then to carbon dioxide. These oxidations provide a source of energy, in some species the CO2 thus generated can be assimilated into biomass. Using the Gram-negative bacterium Paracoccus denitrificans as the experimental model, we infer that oxidation of choline to glycine generates up to three equivalents of formaldehyde and we identify the three steps in the catabolic pathway that are responsible. Our work sheds further light on metabolic pathways that are likely important in a variety of environmental contexts.

microbiology↗

bioRxiv2023

Cancer Prevalence Across Vertebrates

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Petos Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Statement of SignificanceEvolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes.

cancer biology↗

bioRxiv2023

DksA homologs, ppGpp and RegAB regulate dissimilatory nitrogen metabolism in Paracoccus denitrificans

The periplasmic (NAP) and membrane-associated (Nar) nitrate reductases of Paracoccus denitrificans are responsible for nitrate reduction under aerobic and anaerobic conditions, respectively. Expression of NAP is elevated in cells grown on a relatively reduced carbon and energy source (such as butyrate); it is believed that NAP contributes to redox homeostasis by coupling nitrate reduction to the disposal of excess reducing equivalents. Here we show that deletion of either dksA1 (encoding one of two dksA homologs in the P. denitrificans genome) or relA/spoT (encoding a bifunctional ppGpp synthetase and hydrolase) eliminates the butyrate-dependent increase in nap promoter and NAP enzyme activity. We conclude that ppGpp likely signals growth on a reduced substrate and, together with DksA1, mediates increased expression of the genes encoding NAP. Support for this model comes from the observation that nap promoter activity is increased in cultures exposed to a protein synthesis inhibitor that is known to trigger ppGpp synthesis in other organisms. We also show that, under anaerobic growth conditions, the redox-sensing RegAB two-component pair acts as a negative regulator of NAP expression and as a positive regulator of expression of the membrane-associated nitrate reductase Nar. The dksA1 and relA/spoT genes are conditionally synthetically lethal; the double mutant has a null phenotype for growth on butyrate and other reduced substrates while growing normally on succinate and citrate. We also show that the second dksA homolog (dksA2) and relA/spoT have roles in regulation of expression of the flavohemoglobin Hmp and in biofilm formation. IMPORTANCEParacoccus denitrificans is a metabolically versatile Gram-negative bacterium that is used as a model for studies of respiratory metabolism. The organism can utilize nitrate as an electron acceptor for anaerobic respiration, reducing it to dinitrogen via nitrite, nitric oxide, and nitrous oxide. This pathway (known as denitrification) is important as a route for loss of fixed nitrogen from soil and as a source of the greenhouse gas nitrous oxide. Thus, it is important to understand those environmental and genetic factors that govern flux through the denitrification pathway. Here we identify four proteins and a small molecule (ppGpp) which function as previously unknown regulators of expression of enzymes that reduce nitrate and oxidize nitric oxide.

microbiology↗

bioRxiv2022

AI-powered pan-species computational pathology: bridging clinic and wildlife care

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We built the pan-species cancer digital pathology atlas (PANCAD) and conducted the first pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). Furthermore, in 18 other vertebrate species (mammalia=11, reptilia=4, aves=2, and amphibia=1), accuracy (0.57-0.94) was influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. A new metric, named morphospace overlap, was developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on a new understanding of morphological conservation, which could vastly accelerate new developments in veterinary medicine and comparative oncology.

cancer biology↗

bioRxiv2021

Somatic mutation rates scale with lifespan across mammals

The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans. Comparative analyses can shed light on the diversity of mutagenesis across species and on long-standing hypotheses regarding the evolution of somatic mutation rates and their role in cancer and ageing. Here, we used whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found somatic mutagenesis to be dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans, although the relative contribution of each signature varied across species. Remarkably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied displaying a comparable association. Despite widely different life histories among the species surveyed, including [~]30-fold variation in lifespan and [~]40,000-fold variation in body mass, the somatic mutation burden at the end of lifespan varied only by a factor of [~]3. These data unveil common mutational processes across mammals and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.

genomics↗