Deglaciation of Fennoscandia

To provide a new reconstruction of the deglaciation of the Fennoscandian Ice Sheet, in the form of calendar-year time-slices, which are particularly useful for ice sheet modelling, we have compiled and synthesized published geomorphological data for eskers, ice-marginal formations, lineations, marginal meltwater channels, striae, ice-dammed lakes, and geochronological data from radiocarbon, varve, optically-stimulated luminescence, and cosmogenic nuclide dating. This 25 is summarized as a deglaciation map of the Fennoscandian Ice Sheet with isochrons marking every 1000 years between 22 and 13 cal kyr BP and every hundred years between 11.6 and final ice decay after 9.7 cal kyr BP. Deglaciation patterns vary across the Fennoscandian Ice Sheet domain, reflecting differences in climatic and geomorphic settings as well as ice sheet basal thermal conditions and terrestrial versus marine margins. For example, the ice sheet margin in the high-precipitation coastal setting of the western sector responded sensitively to climatic variations leaving a detailed record of prominent moraines and ice-marginal deposits in many fjords and coastal valleys. Retreat rates across the southern sector differed between slow retreat of the terrestrial margin in western and southern Sweden and rapid retreat of the calving ice margin in the Baltic Basin. Our reconstruction is consistent with much of the published research. However, the synthesis of a large amount of existing and new data support refined reconstructions in some areas. For example, we locate the LGM extent of the ice sheet in northwestern Russia further east than previously suggested and conclude that it occurred at a later time than the rest of the ice sheet, at around 17-15 cal kyr BP, and propose a slightly different chronology of moraine formation over southern Sweden based on improved correlations of moraine segments using new LiDAR data and tying the timing of moraine formation to Greenland ice core cold stages. Retreat rates vary by as much as an order of magnitude in different sectors of the ice sheet, with the lowest rates on the high-elevation and maritime Norwegian margin. Retreat rates compared to the climatic information provided by the Greenland ice core record show a general correspondence between retreat rate and climatic forcing, although a close match between retreat rate and climate is unlikely because of other controls, such as topography and marine versus terrestrial margins. Overall, the time slice reconstructions of Fennoscandian Ice Sheet deglaciation from 22 to 9.7 cal kyr BP provide an important dataset for understanding the contexts that underpin spatial and temporal patterns in retreat of the Fennoscandian Ice Sheet, and are an important resource for testing and refining ice sheet models

Rapid post-glacial bedrock weathering in coastal Norway

Quantifying bedrock weathering rates under diverse climate conditions is essential to understanding timescales of landscape evolution. Yet, weathering rates are often difficult to constrain, and associating a weathered landform to a specific formative environment can be complicated by overprinting of successive processes and temporally varying climate. In this study, we investigate three sites between 59°N and 69°N along the Norwegian coast that display grussic saprolite, tafoni, and linear weathering grooves on diverse lithologies. These weathering phenomena have been invoked as examples of geomorphic archives predating Quaternary glaciations and consequently as indicators of minimal glacial erosion. Here we apply cosmogenic nuclide chronometry to assess the recent erosional history. Our results demonstrate that all three sites experienced sufficient erosion to remove most cosmogenic nuclides formed prior to the Last Glacial Maximum. This finding is inconsistent with preservation of surficial (<1–2 m) weathered landforms under non-erosive ice during the last glacial period, while simultaneously demonstrating that post-glacial weathering and erosion rates can be locally rapid (4–10 cm kyr−1) in cold temperate to subarctic coastal locations

B cell receptor repertoire kinetics after SARS-CoV-2 infection and vaccination

B cells are important in immunity to both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyze serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients and find the global BCR repertoire differs between them. Following infection, immunoglobulin (Ig)G1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases, and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination, the proportion of IgD/M BCRs increase, SHM is unchanged, and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, while a more focused response after vaccination mainly targets the spike's receptor-binding domain. Thus, the nature of SARS-CoV-2 exposure differentially affects BCR repertoire development, potentially informing vaccine strategies

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients

Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

William Lockwood and colleagues show that the focal amplification of a gene, BRF2, on Chromosome 8p12 plays a key role in squamous cell carcinoma of the lung

Effective control of sars-cov-2 transmission between healthcare workers during a period of diminished community prevalence of covid-19

Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to nearzero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely

Growth, cell division and sporulation in mycobacteria

Bacteria have the ability to adapt to different growth conditions and to survive in various environments. They have also the capacity to enter into dormant states and some bacteria form spores when exposed to stresses such as starvation and oxygen deprivation. Sporulation has been demonstrated in a number of different bacteria but Mycobacterium spp. have been considered to be non-sporulating bacteria. We recently provided evidence that Mycobacterium marinum and likely also Mycobacterium bovis bacillus Calmette–Guérin can form spores. Mycobacterial spores were detected in old cultures and our findings suggest that sporulation might be an adaptation of lifestyle for mycobacteria under stress. Here we will discuss our current understanding of growth, cell division, and sporulation in mycobacteria

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3-week period (April 2020), 1,032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) &gt;7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B·1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff

Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications

Combined Point-of-Care Nucleic Acid and Antibody Testing for SARS-CoV-2 following Emergence of D614G Spike Variant

Rapid COVID-19 diagnosis in the hospital is essential, although this is complicated by 30%–50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant dominates the pandemic and it is unclear how serological tests designed to detect anti-spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild-type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95% CI 57.8–92.9) by rapid NAAT alone. The combined point of care antibody test and rapid NAAT is not affected by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity