Trace-element abundances in the shallow lithospheric mantle of the North Atlantic Craton margin: implications for melting and metasomatism beneath Northern Scotland

Bulk rock geochemistry and major- and trace-element compositions of clinopyroxene have been determined for three suites of peridotitic mantle xenoliths from the North Atlantic Craton (NAC) in northern Scotland, to establish the magmatic and metasomatic history of subcontinental lithospheric mantle (SCLM) below this region. Spinel lherzolites from the southernmost locality (Streap Com'laidh) have non-NAC mantle compositions, while the two northern xenolith suites (Loch Roag and Rinibar) are derived from the thinned NAC marginal keel. Clinopyroxene compositions have characteristic trace-element signatures which show both 'primary' and 'metasomatic' origins. We use Zr and Hf abundances to identify ancient cryptic refertilization in 'primary' clinopyroxenes. We suggest that Loch Roag and Rinibar peridotite xenoliths represent an ancient Archaean-Palaeoproterozoic SCLM with original depleted cratonic signatures which were overprinted by metasomatism around the time of intrusion of the Scourie Dyke Swarm (∼2.4 Ga). This SCLM keel was preserved during Caledonian orogenesis, although some addition of material and/or metasomatism probably also occurred, as recorded by Rinibar xenoliths. Rinibar and Streap xenoliths were entrained in Permo-Carboniferous magmas and thus were isolated from the SCLM ∼200 Ma before Loch Roag xenoliths (in an Eocene dyke). Crucially, despite their geographical location, lithospheric mantle peridotite samples from Loch Roag show no evidence of recent melting or refertilization during the Palaeogene opening of the Atlantic

The Weaklaw Vent, SE Scotland:Metasomatism of eruptive products by carbo-hydro-fluids of probable mantle origin

This is the author accepted manuscript. The final version is available from CUP via the DOI in this record The Weaklaw vent in SE Scotland (East Lothian coast), inferred to be Namurian, produced lava spatter and volcanic bombs. The latter commonly contained ultramafic xenoliths. All were metasomatised by carbonic fluids rich in incompatible elements. The lavas and xenoliths are inferred to have been basanites and lherzolites prior to metasomatism. The abundance and size of (carbonated) peridotite xenoliths at Weaklaw denotes unusual rapidity of magma ascent and high-energy eruption making Weaklaw exceptional in the British Isles. The lavas and xenoliths were altered subsequently by low-temperature (<200°C) carbo-hydrous fluids to carbonate, clay and quartz assemblages. A small irregular tuffisite 'dyke' that transects the ejecta is also composed dominantly of carbonates and clays. The peridotitic xenoliths are typically foliated, interpreted as originating as pre-entrainment mantle shear-planes. Analyses of the relic spinels shows them to be compositionally similar to spinels in local unaltered lherzolites from near-by basanitic occurrences. Chromium showed neither significant loss nor gain but was concentrated in a di-octahedral smectite allied to volkonskoite. It is in the complex association of smectite with other clays, chlorite and possibly fuchsite that the diverse incompatible elements are concentrated. We conclude that late Palaeozoic trans-tensional fault movement caused mantle shearing. Rapid ascent of basanite magma entrained large quantities of sheared lithospheric mantle. This was followed by ascent of an aggressive carbonate-/ hydroxyl-rich fluid causing pervasive metasomatism. The vent is unique in several ways: in its remarkable clay mineralogy and in displaying such high Cr-clays in a continental intra-plate setting; in being more productive in terms of its 'cargo' of peridotite xenoliths; in presenting an essentially un-eroded sequence of Namurian extrusives; and, not least, for giving evidence for post-eruptive, surface release of small-melt, deep-source fluids

The Complete Genome Sequence of Escherichia coli EC958: A High Quality Reference Sequence for the Globally Disseminated Multidrug Resistant E. coli O25b:H4-ST131 Clone

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage

Donepezil Impairs Memory in Healthy Older Subjects: Behavioural, EEG and Simultaneous EEG/fMRI Biomarkers

Rising life expectancies coupled with an increasing awareness of age-related cognitive decline have led to the unwarranted use of psychopharmaceuticals, including acetylcholinesterase inhibitors (AChEIs), by significant numbers of healthy older individuals. This trend has developed despite very limited data regarding the effectiveness of such drugs on non-clinical groups and recent work indicates that AChEIs can have negative cognitive effects in healthy populations. For the first time, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil) on cognition in healthy older participants. The short- and long-term impact of donepezil was assessed using two double-blind, placebo-controlled trials. In both cases, we utilised cognitive (paired associates learning (CPAL)) and electrophysiological measures (resting EEG power) that have demonstrated high-sensitivity to age-related cognitive decline. Experiment 1 tested the effects of 5 mg/per day dosage on cognitive and EEG markers at 6-hour, 2-week and 4-week follow-ups. In experiment 2, the same markers were further scrutinised using simultaneous EEG/fMRI after a single 5 mg dose. Experiment 1 found significant negative effects of donepezil on CPAL and resting Alpha and Beta band power. Experiment 2 replicated these results and found additional drug-related increases in the Delta band. EEG/fMRI analyses revealed that these oscillatory differences were associated with activity differences in the left hippocampus (Delta), right frontal-parietal network (Alpha), and default-mode network (Beta). We demonstrate the utility of simple cognitive and EEG measures in evaluating drug responses after acute and chronic donepezil administration. The presentation of previously established markers of age-related cognitive decline indicates that AChEIs can impair cognitive function in healthy older individuals. To our knowledge this is the first study to identify the precise neuroanatomical origins of EEG drug markers using simultaneous EEG/fMRI. The results of this study may be useful for evaluating novel drugs for cognitive enhancement

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Peralkaline syenite autoliths from Kilombe volcano, Kenya Rift Valley : evidence for subvolcanic interaction with carbonatitic fluids.

Mineral chemistry, textures and geochemistry of syenite autoliths from Kilombe volcano indicate that they crystallized in the upper parts of a magma chamber from peralkaline trachytic magmas that compositionally straddle the alkali feldspar join in the “residuum system” (ne = 0–1.03; qz = 0–0.77). Mineral reaction and/or overgrowth processes were responsible for the replacement of (i) Mg–hedenbergite by aegirine–augite, Ca–aegirine and/or aegirine, (ii) fayalite by amphiboles, and (iii) magnetite by aenigmatite. Ti–magnetite in silica-saturated syenites generally shows ilmenite exsolution, partly promoted by circulating fluids. By contrast, the Fe–Ti oxides in the silica-undersaturated (sodalite-bearing) syenites show no signs of deuteric alteration. These syenites were ejected shortly after completion of crystallization. Ilmenite–magnetite equilibria indicate fO2 between − 19.5 and − 23.1 log units (T 679–578 °C), slightly below the FMQ buffer. The subsequent crystallization of aenigmatite and Na-rich pyroxenes suggests an increase in the oxidation state of the late-magmatic liquids and implies the influence of post-magmatic fluids. Irrespective of silica saturation, the syenites can be divided into (1) “normal” syenites, characterized by Ce/Ce ratios between 0.83 and 0.99 and (2) Ce-anomalous syenites, showing distinct negative Ce-anomalies (Ce/Ce 0.77–0.24). “Normal” silica-saturated syenites evolved towards pantelleritic trachyte. The Ce-anomalous syenites are relatively depleted in Zr, Hf, Th, Nb and Ta but, with the exception of Ce, are significantly enriched in REE. The silica-saturated syenites contain REE–fluorcarbonates (synchysite-bastnaesite series) with negative Ce-anomalies (Ce/Ce 0.4–0.8, mean 0.6), corroded monazite group minerals with LREE-rich patches, and hydrated, Fe- and P-rich phyllosilicates. Each of these is inferred to be of non-magmatic origin. Fractures in feldspars and pyroxenes contain Pb-, REE- and Mn-rich cryptocrystalline or amorphous material. The monazite minerals are characterized by the most prominent negative Ce-anomalies (Ce/Cemean = 0.5), and in the most altered and Ca-rich areas (depleted in REE), Ce/Ce is less than 0.2. It is inferred that carbonatitic fluids rich in F, Na and lanthanides but depleted in Ce by fractional crystallization of cerian pyrochlore, percolated into the subvolcanic system and interacted with the syenites at the thermal boundary layers of the magma chamber, during and shortly after their crystallization. Chevkinite–(Ce), pyrochlore, monazite and synchysite-bastnaesite, occurring as accessory minerals, have been found for the first time at Kilombe together with eudialyte, nacareniobsite–(Ce) and thorite. These latter represent new mineral occurrences in Kenya

Age and origin of deep crustal meta-igneous xenoliths from the Scottish Midland Valley: vestiges of an Early Palaeozoic Arc and ‘Newer Granite’ magmatism

Deep crustal felsic xenoliths from classic Scottish Midland Valley localities, carried to the surface by Permo-Carboniferous magmatism, are shown for the first time to include metaigneous varieties with dioritic and tonalitic protoliths. Four hypotheses regarding their origin have been evaluated: (1) Precambrian basement; (2) Permo-Carboniferous underplating; (3) ‘Newer Granite’ magmatism; (4) Ordovician arc magmatism. U–Pb zircon dating results rule out the Precambrian basement and Permo-Carboniferous underplating hypotheses, but establish that the meta-igneous xenoliths represent both ‘Newer Granite’ and Ordovician (to possibly Silurian) arc magmatism. The metadiorite xenoliths are shown to have protolith ages of c. 415 Ma with εHft zircon values ranging from +0·1 to +11·1. These are interpreted to represent unexposed ‘Newer Granite’ plutons, based on age, mineralogical, isotopic and geochemical data. This shows that Devonian ‘Newer Granite’ magmatism had a greater impact on the Midland Valley and Southern Uplands crust than previously realized. Clinopyroxene–plagioclase–quartz barometry on the metadiorites from the east and west of the Midland Valley yielded a similar pressure range of c. 5–10 kbar, and a metadiorite from the east yielded a minimum two-feldspar temperature estimate of c. 793–816°C. These results indicate that the metadiorites once resided in the middle–lower crust. In contrast, two metatonalite xenoliths have a Late Ordovician protolith age (c. 453 Ma), with zircon εHft values of +7·8 to +9·0. These are interpreted as samples of a buried Late Ordovician magmatic arc situated within the Midland Valley. Inherited zircons with similar Late Ordovician ages and εHft=453 values (+1·6 to +10·8) are present in the metadiorites, suggesting that the Devonian ‘Newer Granites’ intruded within or through this Late Ordovician Midland Valley arc. A younger protolith age of c. 430 Ma from one of the metatonalites suggests that arc activity continued until Silurian times. This validates the long-standing ‘arc collision’ hypothesis for the development of the Caledonian Orogen. Based on U–Pb zircon dating, the metatonalite and metadiorite xenoliths have both experienced metamorphism between c. 400 and c. 391 Ma, probably linked to the Acadian Orogeny. An older phase of metamorphism at c. 411 Ma was possibly triggered by the combined effects of heating owing to the emplacement of the ‘Newer Granite’ plutons and the overthrusting of the Southern Uplands terrane onto the southern margin of the Midland Valley terrane