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Rogers, L.

Publications and source records attributed to Rogers, L..

10 recordsLinked to original sources

3,500 years of sheeppox virus evolution inferred from archaeological and codicological genomes

Sheeppox virus (SPPV) is a major livestock pathogen causing economic hardship through reduced production and death of vulnerable sheep, with written descriptions of sheeppox-like disease recorded since antiquity. We report 21 novel ancient SPPV genomes spanning the Eurasian steppe Bronze Age ([~]1,700 BCE) to the Early Modern period in Western Europe, including multiple genomes obtained from medieval parchment. We estimate that major capripoxvirus lineages diverged [~]11,500-3,700 years ago, overlapping known translocations and bio-cultural developments in sheep. Our dataset supports SPPV diverging first within the lineage leading to goatpox virus and lumpy skin disease virus, and that known gene inactivation events within SPPV and goatpox virus occur in our earliest SPPV genomes. These findings reveal that the food security of Eurasian communities have been threatened by sheeppox for over 3,700 years, and provide new insights to the genomic evolution and potential host adaptation of sheeppox virus. TeaserAncient viral genomes from manuscripts and teeth illuminate the evolutionary history of sheeppox virus.

genetics↗

Hierarchical processing and polarization encoding in the cephalopod visual system

Coleoid cephalopods (octopus, cuttlefish and squid, hereafter cephalopods) have evolved a range of complex visually-guided behaviours, from dexterous hunting to skin-pattern based camouflage and communication1. They have also evolved sensitivity to the polarization of light2, an adaptation thought to help detect camouflaged or semitransparent predators and prey in low visibility underwater environments3-10. How visual information is processed by the cephalopod brain to support their behaviours remains unclear. Here, studying the bigfin reef squid Sepioteuthis lessoniana, we performed calcium imaging and electrophysiological recordings from populations of neurons in the large visual center of the cephalopod brain, the optic lobe (OL). We revealed that the retina-recipient superficial OL contains a diversity of functionally distinct cell types, spatially organized into sub-layers, processing spatio-temporal features of light intensity and possessing polarization angle specificity. More complex features, e.g. direction selectivity, are seen in deeper regions of the OL cortex, which also exhibits spontaneous waves of neural activity in the absence of visual input. Neurons in the downstream OL medulla exhibit visual receptive field sizes and spontaneous activity levels which increase with brain depth, consistent with the hierarchical processing of visual information through the medullas tree-like anatomical organization. Medulla neurons exhibit sensitivity to local decreases in the degree of linear polarization (DoLP), which they integrate additively with light intensity information. Underwater imaging in the squids habitat off the coast of Okinawa, Japan, demonstrate that polarization sensitivity confers a robust short-range boost in object-background contrast over a range of objects and environmental conditions. These findings reveal convergent principles of hierarchical visual processing shared between cephalopods and vertebrates, and highlight how cephalopods utilise their distinct adaptation of polarization sensitivity to solve universal visual challenges underwater.

neuroscience↗

A nonhuman primate model mirrors human congenital cytomegalovirus infection and reveals a spectrum of vertical transmission outcomes

Congenital cytomegalovirus (cCMV) is the leading infectious cause of birth defects worldwide, yet immune determinants of protection to inform design of a maternal vaccine remain elusive. Here, we characterized the outcome of primary rhesus CMV (RhCMV) infection during pregnancy in an immune competent nonhuman primate (NHP) model. RhCMV DNA was detected in amniotic fluid and/or fetal tissues in six of 12 (50% placental transmission) CMV-naive rhesus macaque dams inoculated intravenously with RhCMV in early second trimester gestation. Widespread tissue dissemination dominated by one of two inoculated RhCMV strains was present in one fetus (8.3% cCMV disease). Placental RhCMV transmission was associated with elevated fetal and maternal plasma TNF-alpha and reduced maternal brain-derived neurotrophic factor and IL-10 levels. CMV exposure during pregnancy had a broad impact on the placenta and fetus even in the absence of congenital infection as evidenced by RhCMV infection at the maternal-fetal interface in all 12 dams, along with significantly reduced placental efficiency and fetal growth metrics compared to gestation-matched control pregnancies. This NHP model recapitulates key aspects of human cCMV and provides new insight into barriers and biomarkers of successful vertical transmission. One sentence summary: The nonhuman primate model mirrors the epidemiology of human congenital CMV (cCMV) after primary infection and reveals its transmission bottlenecks.

immunology↗

Hybrid xyloglucan utilisation loci are prevalent among plant-associated Bacteroidota

The plant hemicellulose xyloglucan (XyG) is secreted from the roots of numerous plant species, including cereals, and contributes towards soil aggregate formation in terrestrial systems. Whether XyG represents a key nutrient for plant-associated bacteria is unclear. The phylum Bacteroidota are abundant in the plant microbiome and provide several beneficial functions for their host. However, the metabolic and genomic traits underpinning their success remain poorly understood. Here, using proteomics, bacterial genetics, and genomics, we revealed that plant-associated Flavobacterium, a genus within the Bacteroidota, can efficiently utilise XyG through the occurrence of a distinct and conserved gene cluster, referred to as the Xyloglucan Utilisation Loci (XyGUL). Flavobacterium XyGUL is a hybrid of the molecular machinery found in gut Bacteroides spp., Cellvibrio japonicus, and the plant pathogen Xanthomonas. Combining protein biochemistry, computational modelling and phylogenetics, we identified a mutation in the enzyme required for initiating hydrolysis of the XyG polysaccharide, an outer membrane endoxyloglucanase glycoside hydrolase family 5 subfamily 4 (GH5_4), which enhances activity towards XyG. A subclade of GH5_4 homologs carrying this mutation were the dominant form found in soil and plant metagenomes due to their occurrence in Bacteroidota and Proteobacteria. However, only in members of the Bacteroidota spp., particularly Flavobacterium spp. was such a remarkable degree of XyGUL conservation detected. We propose this mechanism enables plant-associated Flavobacterium to specialise in competitive acquisition of XyG exudates and that this hemicellulose may represent an important nutrient source, enabling them to thrive in the plant microbiome, which is typified by intense competition for low molecular weight carbon exudates.

microbiology↗

Ancient Mongolian aurochs genomes reveal sustained introgression and management in East Asia

Societies in East Asia have utilized domesticated cattle for over 5000 years, but the genetic history of cattle in East Asia remains understudied. Genome-wide analyses of 23 ancient Mongolian cattle reveal that East Asian aurochs and ancient East Asian taurine cattle are closely related, but neither are closely related to any modern East Asian breeds. We observe binary variation in aurochs diet throughout the early Neolithic, and genomic evidence shows millennia of sustained male-dominated introgression. We identify a unique connection between ancient Mongolian aurochs and the European Hereford breed. These results point to the likelihood of human management of aurochs in Northeast Asia prior to and during the initial adoption of taurine cattle pastoralism. One-Sentence SummaryAncient interbreeding of East Asian aurochs and cattle suggests management, but leaves no signature in modern eastern breeds.

genomics↗

Finding coarse and fine scale population structure in a coastal species: population demographics meets genomics

Population genetic studies often focus on patterns at a regional scale and use spatially aggregated samples to draw inferences about population structure and drivers, potentially masking ecologically relevant population sub-structure and dynamics. In this study we use a multidisciplinary approach combining genomic, demographic, and habitat data with an oceanographic particle drift model, to unravel the patterns of genetic structure at different scales in the black goby (Gobius niger) along the Norwegian coast. Using a high-density sampling protocol, we observed restricted gene flow both at a surprisingly fine (kms) and large (100s km) scale. Our results showed a pattern of isolation by distance related to the level of exposure along the Skagerrak coast, where sheltered sampling stations had an overall level of genetic divergence about three times higher (FST =0.0046) than levels observed among exposed samples (FST =0.0015). These results were corroborated by demographic analyses which showed that population-fluctuations decrease in synchrony with distance at much smaller scales for sheltered samples (20 km) than for exposed sites (80 km), suggesting higher population connectivity among exposed sites. We also found a pronounced genetic discontinuity between populations along the Norwegian west and east coasts, with a sharp "break" around the southern tip of Norway, likely driven both by lack of habitat and by oceanographic features.

genomics↗

DNA methylation and survival differences associated with the type of IDH mutation in 1p/19q non-codeleted astrocytomas

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1R132H mutations. This high prevalence is important as IDH1R132H is presumed to be relatively poor at producing D-2-hydroxyglutarate (D-2HG) whereas high concentrations of this oncometabolite are required to inhibit TET2 DNA demethylating enzymes. Indeed, patients harbouring IDH1R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of site of origin. For 1p/19q non-codeleted glioma patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring non-R132H mutated tumours have better outcome (HR 0.41, 95% CI [0.24, 0.71], p=0.0013). Non-R132H mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p<0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H mutated 1p/19q non-codeleted gliomas have a more favourable prognosis than their IDH1R132H mutated counterpart is clinically relevant and should be taken into account for patient prognostication. Single sentence summaryAstrocytoma patients with tumours harbouring IDH mutations other than p.R132H have increased DNA methylation levels and longer survival

cancer biology↗

Single Nucleus Multiomic Profiling Reveals Age-Dynamic Regulation of Host Genes Associated with SARS-CoV-2 Infection

Respiratory failure is the leading cause of COVID-19 death and disproportionately impacts adults more than children. Here, we present a large-scale snATAC-seq dataset (90,980 nuclei) of the human lung, generated in parallel with snRNA-seq (46,500 nuclei), from healthy donors of ~30 weeks, ~3 years and ~30 years of age. Focusing on genes implicated in SARS-CoV-2 cell entry, we observed an increase in the proportion of alveolar epithelial cells expressing ACE2 and TMPRSS2 in adult compared to young lungs. Consistent with expression dynamics, 10 chromatin peaks linked to TMPRSS2 exhibited significantly increased activity with age and harbored IRF and STAT binding sites. Furthermore, we identified 14 common sequence variants in age-increasing peaks with predicted regulatory function, including several associated with respiratory traits and TMPRSS2 expression. Our findings reveal a plausible contributor to why children are more resistant to COVID-19 and provide an epigenomic basis for transferring this resistance to older populations.

genomics↗

Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages

IntroductionThere is an increasing prevalence of non-communicable diseases worldwide. Metabolic diseases such as obesity and gestational diabetes mellitus (GDM) increasingly affect women during pregnancy, which can harm pregnancy outcomes and the long-term health and wellbeing of exposed offspring. Both obesity and GDM have been associated with proinflammatory effects within the placenta, the critical organ governing fetal development.\n\nMethodsThe purpose of these studies was to model, in vitro, the effects of metabolic stress (high levels of glucose, insulin and saturated lipids) on placental macrophage biology, since these cells are the primary innate immune phagocyte within the placenta with roles in governing maternofetal immune tolerance and antimicrobial host defense. Macrophages were isolated from the villous core of term, human placentae delivered through nonlaboring, elective Cesarean sections and exposed to combinations of elevated glucose (30 mM), insulin (10 nM) and the saturated lipid palmitic acid (palmitate, 0.4 mM).\n\nResultsWe found that palmitate alone induced the activation of the nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in placental macrophages, which was associated with increased interleukin 1 beta release and an increase in apoptotic cell death. Glucose and insulin neither provoked these effects nor augmented the impact of palmitate itself.\n\nDiscussionOur findings confirm an impact of saturated fat on placental macrophage immune activation and could be relevant to the impact of metabolic stress in vivo.

immunology↗

When is a fish stock collapsed?

Marine fish stock collapses are a major concern for scientists and society due to the potentially severe impacts on ecosystem resilience, food security and livelihoods. Yet the general state of harvested fish populations has proven difficult to summarize, and the actual occurrence rate of stock collapses remains unclear. We have carried out a literature review and multi-stock analysis to show that numerous definitions exist for classifying stocks as collapsed, and that the classification of a stocks status is sensitive to changes in the collapse definitions formulation. We suggest that the lack of a unified definition has contributed to contrasting perceptions on the state of fish stocks. Therefore, we comprehensively define what constitutes a fish stock collapse and provide a time-series based method for collapse detection. Unlike existing definitions, our definition is process-based, because it links together three important phases of collapse events: the abrupt decline, an ensuing period of prolonged depletion, and potential recovery. Furthermore, these phases are specified in terms of population turnover. Through systematic evaluation, our definition can accurately distinguish collapses from less severe depletions or natural fluctuations for stocks with diverse life histories, helping identify the stocks in greatest need of reparatory measures. Our study advocates the consistent use of definitions to limit both alarmist and conservative narratives on the state of fish stocks, and to promote cooperation between conservation and fisheries scientists. This will facilitate clear and accurate communication of science to both the public and to policy-makers to ensure healthy fish stocks in the future.

ecology↗