Early Middle Pleistocene sediments at Sidestrand, northeast Norfolk, yield the most extensive preglacial cold stage beetle assemblage from Britain

Fluvial sediments (Cromer Forest-bed Formation) at Sidestrand, northeast Norfolk, have yielded the most extensive preglacial early Middle Pleistocene cold (arctic) stage beetle assemblage known from Britain. The assemblage is composed of 59 taxa indicating severely cold and continental climatic conditions. Mutual Climatic Range reconstructions suggest that the mean temperature of the warmest month (July) was between 10 °C and 13 °C and the mean temperature of the coldest months (January and February) between −17 °C and −10 °C, although the actual palaeotemperatures were probably towards the lower end of these ranges. Associated pollen and macroflora remains were poorly represented but all are known from other cold stage contexts. Excavations reveal that this freshwater arctic assemblage occurs within units between two important stratigraphic marker horizons, the Sidestrand Hall Member of the Cromer Forest-bed Formation and the first lowland glacigenic deposit (Happisburgh Till Member) in eastern England, although the ages of both remain equivocal. Recent amino-acid chronologies of molluscan faunas from the Sidestrand Hall Member indicate a MIS 13 age, with by inference a MIS 12 age for the overlying arctic units with cold beetle fauna and for the Happisburgh Till Member. However, the arctic units are separated from the two stratigraphic marker horizons by shallow marine deposits (Wroxham Crag Formation) demonstrating at least two intervening phases of marine transgression and a cold climate marine regression. The climatic significance of these marine transgressions and their chronostratigraphic implications are currently uncertain

Late Quaternary sea-level changes of the Persian Gulf

Late Quaternary reflooding of the Persian Gulf climaxed with the mid-Holocene highstand previously variously dated between 6 and 3.4 ka. Examination of the stratigraphic and paleoenvironmental context of a mid- Holocenewhale beaching allows us to accurately constrain the timing of the transgressive, highstand and regressive phases of the mid- to late Holocene sea-level highstand in the Persian Gulf. Mid-Holocene transgression of the Gulf surpassed today's sea level by 7100–6890 cal yr BP, attaining a highstand of N1 m above current sea level shortly after 5290–4570 cal yr BP before falling back to current levels by 1440–1170 cal yr BP. The cetacean beached into an intertidal hardground pond during the transgressive phase (5300–4960 cal yr BP) with continued transgression interring the skeleton in shallow-subtidal sediments. Subsequent relative sea-level fall produced a forced regression with consequent progradation of the coastal system. These new ages refine previously reported timings for the mid- to late Holocene sea-level highstand published for other regions. By so doing, they allow us to constrain the timing of this correlatable global eustatic event more accurately

Excavating the ‘Rutland Sea Dragon’: The largest ichthyosaur skeleton ever found in the UK (Whitby Mudstone Formation, Toarcian, Lower Jurassic)

An almost complete ichthyosaur skeleton 10 m long was discovered in January 2021 at the Rutland Water Nature Reserve in the county of Rutland, UK. This was excavated by a small team of palaeontologists in the summer of the same year. Nicknamed ‘The Rutland Sea Dragon’, this almost fully articulated skeleton is an example of the large-bodied Early Jurassic ichthyosaur Temnodontosaurus. The specimen was analysed in situ, recorded (including a 3D scan using photogrammetry), excavated and removed from the site in a series of large plaster field jackets to preserve taphonomic information. Significantly, the specimen is the largest ichthyosaur skeleton to have been found in the UK and it may be the first recorded example of Temnodontosaurus trigonodon to be found in the country, extending its known geographic range significantly. It also represents the most complete skeleton of a large prehistoric reptile to have been found in the UK. We provide an account of the discovery and describe the methods used for excavating, recording and lifting the large skeleton which will aid palaeontologists facing similar challenges when collecting extensive remains of large and fragile fossil vertebrates. We also discuss the preliminary research findings and the global impact this discovery has had through public engagement

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

First dinosaur from the Isle of Eigg (Valtos Sandstone Formation, Middle Jurassic) Scotland

Dinosaur body fossil material is rare in Scotland, previously known almost exclusively from the Great Estuarine Group on the Isle of Skye. We report the first unequivocal dinosaur fossil from the Isle of Eigg, belonging to a Bathonian (Middle Jurassic) taxon of uncertain affinity. The limb bone NMS G.2020.10.1 is incomplete, but through a combination of anatomical comparison and osteohistology, we determine it most likely represents a stegosaur fibula. The overall proportions and cross-sectional geometry are similar to the fibulae of thyreophorans. Examination of the bone microstructure reveals a high degree of remodelling and randomly distributed longitudinal canals in the remaining primary cortical bone. This contrasts with the histological signal expected of theropod or sauropod limb bones, but is consistent with previous studies of thyreophorans, specifically stegosaurs. Previous dinosaur material from Skye and broadly contemporaneous sites in England belongs to this group, including <jats:italic>Loricatosaurus</jats:italic> and <jats:italic>Sarcolestes</jats:italic> and a number of indeterminate stegosaur specimens. Theropods such as <jats:italic>Megalosaurus</jats:italic> and sauropods such as <jats:italic>Cetiosaurus</jats:italic> are also known from these localities. Although we find strong evidence for a stegosaur affinity, diagnostic features are not observed on NMS G.2020.10.1, preventing us from referring it to any known genera. The presence of this large-bodied stegosaur on Eigg adds a significant new datapoint for dinosaur distribution in the Middle Jurassic of Scotland

A New Threat to Honey Bees, the Parasitic Phorid Fly Apocephalus borealis

Honey bee colonies are subject to numerous pathogens and parasites. Interaction among multiple pathogens and parasites is the proposed cause for Colony Collapse Disorder (CCD), a syndrome characterized by worker bees abandoning their hive. Here we provide the first documentation that the phorid fly Apocephalus borealis, previously known to parasitize bumble bees, also infects and eventually kills honey bees and may pose an emerging threat to North American apiculture. Parasitized honey bees show hive abandonment behavior, leaving their hives at night and dying shortly thereafter. On average, seven days later up to 13 phorid larvae emerge from each dead bee and pupate away from the bee. Using DNA barcoding, we confirmed that phorids that emerged from honey bees and bumble bees were the same species. Microarray analyses of honey bees from infected hives revealed that these bees are often infected with deformed wing virus and Nosema ceranae. Larvae and adult phorids also tested positive for these pathogens, implicating the fly as a potential vector or reservoir of these honey bee pathogens. Phorid parasitism may affect hive viability since 77% of sites sampled in the San Francisco Bay Area were infected by the fly and microarray analyses detected phorids in commercial hives in South Dakota and California's Central Valley. Understanding details of phorid infection may shed light on similar hive abandonment behaviors seen in CCD

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care