Kinship in Aegean Prehistory? Ancient DNA in Human Bones from Mainland Greece and Crete

Attempts were made to detect ancient DNA (aDNA) in samples of 89 human skeletons from Neolithic and Bronze Age sites in Greece and Crete. Ancient DNA was absent in specimens from Nea Nicomedia, Lerna, Kato Zakro: Karaviádena, and Mycenae Grave Circle A. For each of three skeletons sampled from Antron Grave Circle B, polymerase chain reactions (PCRs) gave products for nuclear but not mitochondrial DNA, but the yield of DNA was low and inconsistent, with replicate PCRs failing to give reproducible results. At Kouphovouno evidence for mitochondrial and/or nuclear aDNA was obtained from eight of the 20 skeletons that were examined, while at Mycenae Grave Circle B evidence for mitochondrial aDNA was obtained for four of the 22 skeletons that were studied, and in two cases confirmed the evidence of close kinship that had already been suggested by facial reconstruction: this in turn raises interesting questions of social relationships and the role of high-status women in MBA/LBA society. We conclude that, although aDNA might be present in some Eastern Mediterranean skeletons from later centuries of the Bronze Age, it is not commonly found in material from this period and is likely to be absent from older material.Στη μελέτη αυτή έγιναν προσπάθειες να αναγνωριστεί αρχαίο DNA (aDNA) σε δείγματα ογδόντα εννέα ανθρώπινων σκελετών προερχομένων από θέσεις της Νεολιθικής περιόδου και της Εποχής του Χαλκού στην Ελλάδα και την Κρήτη. Αρχαίο DNA δεν εντοπίστηκε σε δείγματα από τη Νέα Νικομήδεια, τη Λέρνα, την Κάτω Ζάκρο (Καραβιάδενα) και τον Ταφικό Κύκλο Α των Μυκηνών. Για κάθε έναν από τους τρεις σκελετούς, οι οποίοι εξετάστηκαν από τον Ταφικό Κύκλο Β της Αντρώνας, οι αλυσιδωτές αντιδράσεις πολυμεράσης (PCRs) απέφεραν αποτελέσματα για πυρηνικό αλλά όχι μιτοχονδριακό DNA. Η παραγωγή DNA ήταν χαμηλή και αντιφατική, με τα αντίγραφα πολυμεράσης να αποτυγχάνουν να αποφέρουν αναπαραγώγιμα αποτελέσματα. Στο Κουφόβουνο οκτώ από τους είκοσι σκελετούς, που εξετάστηκαν, έδωσαν στοιχεία για μιτοχονδρνακό ή/και πυρηνικό DNA, ενώ στον Ταφικό Κύκλο Β των Μυκηνών ενδείξεις για μιτοχονδριακό DNA έδωσαν τέσσερεις από τους είκοσι δύο σκελετούς, που μελετήθηκαν. Σε δύο περιπτώσεις επιβεβαιώθηκε η ένδειξη στενής συγγένειας, κάτι το οποίο είχε ήδη προταθεί με την αποκατάσταση των προσώπων: το γεγονός αυτό εγείρει ενδιαφέροντα ερωτήματα σχετικά με τις κοινωνικές σχέσεις και το ρόλο γυναικών υψηλής κοινωνικής στάθμης στην κοινωνία της Μέσης και της Ύστερης Εποχής του Χαλκού. Συμπεραίνουμε ότι, αν και μπορεί να αναγνωριστεί DNA σε ορισμένους σκελετούς της Ανατολικής Μεσογείου των τελευταίων αιώνων της Εποχής του Χαλκού, δεν εντοπίζεται συχνά σε υλικό αυτής της εποχής και ενδεχομένως απουσιάζει από παλαιότερο υλνκό.</jats:p

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Brief communication: identification of the authentic ancient DNA sequence in a human bone contaminated with modern DNA

We present a method to distinguish authentic ancient DNA from contaminating DNA in a human bone. This is achieved by taking account of the spatial distribution of the various sequence families within the bone and the extent of degradation of the template DNAs, as revealed by the error content of the sequences. To demonstrate the veracity of the method, we handled two ancient human tibiae in order to contaminate them with modern DNA, and then subjected segments of the bones to various decontaminating treatments, including removal of the outer 1-2 mm, before extracting DNA, cloning, and obtaining a total of 107 mitochondrial DNA sequences. Sequences resulting from the deliberate contamination were located exclusively in the outer 1-2 mm of the bones, and only one of these 27 sequences contained an error that could be ascribed to DNA degradation. A second, much smaller set of relatively error-free sequences, which we ascribe to contamination during excavation or curation, was also located exclusively in the outer 1-2 mm. In contrast, a family of 72 sequences, displaying extensive degradation products but identifiable as haplogroup U5a1a, was distributed throughout one of the bones and represents the authentic ancient DNA content of this specimen

Regulation of ICAM-1 in human neutrophils.

Intercellular cell adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein with a vital role in the immune response to pathogens. The expression pattern of ICAM-1 is wide-ranging, encompassing endothelial cells, epithelial cells and neutrophils. Recent work has characterized the role of ICAM-1 in murine neutrophils, but the function of human neutrophil ICAM-1 is incompletely understood. Herein, we investigated the expression and role of ICAMs in human neutrophils in vitro and in vivo. Our findings show clear expression of ICAM-1, -3 and -4 on peripheral blood-derived neutrophils and demonstrate that the pathogen-associated molecular pattern (PAMP) lipoteichoic acid (LTA) is an inducer of ICAM-1 expression in vitro. In vivo, neutrophils obtained from the pleural cavity of patients with a parapneumonic effusion display enhanced expression of ICAM-1 compared to peripheral blood- and oral cavity-derived neutrophils. Moreover, migration of peripheral blood-derived neutrophils across endothelial cells can upregulate neutrophil ICAM-1 expression. These findings indicate that PAMPs and/or cytokines, alongside transmigration, enhance neutrophil ICAM-1 expression at sites of inflammation. Mechanistically we observed that ICAM-1high neutrophils display elevated S. aureus phagocytic capacity. However, unlike murine neutrophils, ICAM-1 intracellular signaling in human neutrophils was not essential for phagocytosis of S. aureus and reactive oxygen species (ROS) generation. Taken together, these results have important implications for the regulation of neutrophil-mediated pathogen clearance

Hypoxia increases the potential for neutrophil-mediated endothelial damage in COPD

Rationale: Chronic obstructive pulmonary disease (COPD) patients experience excess cardiovascular morbidity and mortality, and exacerbations further increase the risk of such events. COPD is associated with persistent blood and airway neutrophilia, and systemic and tissue hypoxia. Hypoxia augments neutrophil elastase release, enhancing capacity for tissue injury. Objective: To determine whether hypoxia-driven neutrophil protein secretion contributes to endothelial damage in COPD. Methods: The healthy human neutrophil secretome generated under normoxic or hypoxic conditions was characterised by quantitative mass spectrometry, and the capacity for neutrophil-mediated endothelial damage assessed. Histotoxic protein levels were measured in normoxic versus hypoxic neutrophil supernatants and plasma from exacerbating COPD patients and healthy controls. Main results: Hypoxia promoted PI3Kγ-dependent neutrophil elastase secretion, with greater release seen in neutrophils from COPD patients. Supernatants from neutrophils incubated under hypoxia caused pulmonary endothelial cell damage and identical supernatants from COPD neutrophils increased neutrophil adherence to endothelial cells. Proteomics revealed differential neutrophil protein secretion under hypoxia and normoxia; hypoxia augmented secretion of a subset of histotoxic granule and cytosolic proteins, with significantly greater release seen in COPD neutrophils. The plasma of COPD patients had higher content of hypoxia-upregulated neutrophil-derived proteins and protease activity, and vascular injury markers. Conclusions: Hypoxia drives a destructive ‘hyper-secretory’ neutrophil phenotype conferring enhanced capacity for endothelial injury, with a corresponding signature of 5 neutrophil degranulation and vascular injury identified in COPD patient plasma. Thus, hypoxic enhancement of neutrophil degranulation may contribute to increased cardiovascular risk in COPD. These insights may identify new therapeutic opportunities for endothelial damage in COPD

Identifying the Science and Technology Dimensions of Emerging Public Policy Issues through Horizon Scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security