The ‘mosaic habitat’ concept in human evolution: past and present

The habitats preferred by hominins and other species are an important theme in palaeoanthropology, and the ‘mosaic habitat’ (also referred to as habitat heterogeneity) has been a central concept in this regard for the last four decades. Here we explore the development of this concept – loosely defined as a range of different habitat types, such as woodlands, riverine forest and savannah within a limited spatial area– in studies of human evolution in the last sixty years or so. We outline the key developments that took place before and around the time when the term ‘mosaic’ came to wider palaeoanthropological attention. To achieve this we used an analysis of the published literature, a study of illustrations of hominin evolution from 1925 onwards and an email survey of senior researchers in palaeoanthropology and related fields. We found that the term mosaic starts to be applied in palaeoanthropological thinking during the 1970’s due to the work of a number of researchers, including Karl Butzer and Glynn Isaac , with the earliest usage we have found of ‘mosaic’ in specific reference to hominin habitats being by Adriaan Kortlandt (1972). While we observe a steady increase in the numbers of publications reporting mosaic palaeohabitats, in keeping with the growing interest and specialisation in various methods of palaeoenvironmental reconstruction, we also note that there is a lack of critical studies that define this habitat, or examine the temporal and spatial scales associated with it. The general consensus within the field is that the concept now requires more detailed definition and study to evaluate its role in human evolution

Evolutionary remodelling of N-terminal domain loops fine-tunes SARS-CoV-2 spike

The emergence of SARS-CoV-2 variants has exacerbated the COVID-19 global health crisis. Thus far, all variants carry mutations in the spike glycoprotein, which is a critical determinant of viral transmission being responsible for attachment, receptor engagement and membrane fusion, and an important target of immunity. Variants frequently bear truncations of flexible loops in the N-terminal domain (NTD) of spike; the functional importance of these modifications has remained poorly characterised. We demonstrate that NTD deletions are important for efficient entry by the Alpha and Omicron variants and that this correlates with spike stability. Phylogenetic analysis reveals extensive NTD loop length polymorphisms across the sarbecoviruses, setting an evolutionary precedent for loop remodelling. Guided by these analyses, we demonstrate that variations in NTD loop length, alone, are sufficient to modulate virus entry. We propose that variations in NTD loop length act to fine-tune spike; this may provide a mechanism for SARS-CoV-2 to navigate a complex selection landscape encompassing optimisation of essential functionality, immune-driven antigenic variation and ongoing adaptation to a new host

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

THE SIGNIFICANCE OF THE CRETACEOUS DIAMONDIFEROUS GRAVEL DEPOSIT AT MAHURA MUTHLA, NORTHERN CAPE PROVINCE, SOUTH AFRICA

Rewbell Jean François. Élection de MM. l’abbé Besse, Fournier de La Charmie et Verchère de Reffye comme secrétaires de l'Assemblée, lors de la séance du 7 mai 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXV - Du 13 avril 1791 au 11 mai 1791. Paris : Librairie Administrative P. Dupont, 1886. p. 658

The significance of the cretaceous diamondiferous gravel deposit at Mahura Muthla, Northern Cape province, South Africa

Remnants of diamond-bearing fluvial gravels of Cretaceous age have been preserved on the Ghaap Plateau north-west of Reivilo at 1455 in above sea level. The alluvial deposit contains well preserved fossil woods representing at least four periods: Post-Permian (Upper Karoo), Early Cretaceous, Late Cretaceous and Tertiary. The Karoo specimen has been derived from Beaufort Group Sediments, now eroded from the Ghaap Plateau. More significant are the presence of Early and Late Cretaceous woods, both periods believed to have been wetter in the interior of southern Africa. In addition to the diamonds, other kimberlite derived minerals such as ilmenite and garnet have also been recovered from these gravels. Detailed mineral chemical analyses of the ilmenites and those occurring in primary sources within a radius of 120 km of the Mahura Muthla area indicate that the most likely source are kimberlites occurring to the south-south-east, indicating that the palaeo-channel was flowing from the south-east to the north-west. This is supported by the presence of ironstone and red chert cobbles and pebbles derived from the Proterozoic Kanguru Member outcropping directly south of the Channel. Further evidence comes from a palaeo-tributary on Laurika which joined the main Mahura Muthla trunk stream from the south-west; limited pebble imbrications; and a decrease in the sizes of wood, agate and ironstone cobbles and pebbles in a northerly direction associated with an increase of roundness of these clasts. At the Start of the Cretaceous the area was covered by sandstones of the Beaufort Group with overlying flood basalts of the Drakensberg Group. First during the Early Cretaceous the Mahura Muthla Channel was incising into an easterly retreating palaeo-escarpment of Karoo basalts. Group 2 kimberlites such as Finch, Darleston and Duivelskop, had already intruded these basalts around 120Ma. The north-westerly orientated drainage was directly linked to the drainage basin of the Kalahari River draining the northern part of the northern Cape and southern Botswana via the palaeo-Molopo and lower Orange River. This period of erosion would have released an abundance of agates from the basalts that are so abundantly present in the gravels and also diamonds from these Group 2 kimberlites. On comparing the mineral chemistry of the ilmenites the most likely source for these kimberlitic minerals is the area to the south east of Mahura Muthla. Kimberlites occurring in this area include the Duivelskop Group, X 154, Pienaarspoort, the Bellsbank Group, Bull Hill and Mayeng. At least some of these could have provided diamonds to the gravels. Later during Upper Cretaceous times the Karoo basalts had been removed and the drainage stripped the remaining Sediments of the Beaufort Group before the sinuous Channel became locked and preserved within the Transvaal dolomites. Subsequently the Channel became calcretised during the development of the African Surface in the Early Tertiary. Mahura Muthla remained part of the Kalahari River basin which fed the Molopo River and the lower Orange drainage network and by the Early Tertiary the latter had captured the Vaal and the upper and middle Orange River drainage basin which had been part of the Karoo River drainage for most of the Cretaceous