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Neither geologists nor biologists have a definition that is capable of classifying Madagascar unambiguously as an island or a continent; nor can they incorporate Malagasy natural history into a single model rooted in Africa or Asia. Madagascar is a microcosm of the larger continents, with a rock record that spans more than 3000 million years (Ma), during which it has been united episodically with, and divorced from, Asian and African connections. This is reflected in its Precambrian history of deep crustal tectonics and a Phanerozoic history of biodiversity that fluctuated between cosmopolitanism and parochialism. Both vicariance and dispersal events over the past 90 Ma have blended a unique endemism on Madagascar, now in decline following rapid extinctions that started about 2000 years ago.

Aim To investigate the validity of Simpson's model of sweepstakes dispersal, particularly as it applies to the colonization of Madagascar by African mammals. We chose lemurs as a classic case. Location The East African coast, the Mozambique Channel and Madagascar. Methods First, we investigated the assumptions underlying Simpson's statistical model as it relates to dispersal events. Second, we modelled the fate of a natural raft carrying one or several migrating mammals under a range of environmental conditions: in the absence of winds or currents, in the presence of winds and currents, and with and without a sail. Finally, we investigated the possibility of an animal being transported across the Mozambique Channel by an extreme climatic event like a tornado or a cyclone. Results Our investigations show that Simpson's assumptions are consistently violated when applied to scenarios of over-water dispersal by mammals. We suggest that a simple binomial probability model is an inappropriate basis for extrapolating the likelihood of dispersal events. One possible alternative is to use a geometric probability model. Our estimates of current and wind trajectories show that the most likely fate for a raft emerging from an estuary on the east coast of Africa is to follow the Mozambique current and become beached back on the African coast. Given prevailing winds and currents, transport from Madagascar to Africa is very much more likely than the reverse process. Freak transport by means of a hurricane or tornado is even less likely than rafting for mammals. Main conclusions Our models suggest that the scenario of sweepstakes dispersal that currently enjoys wide support is not valid at either the theoretical or the applied level when applied to the hypothetical invasion of Madagascar by African mammals. Alternative explanations should be sought.

Organic materials across the palynologically defined Permian-Triassic (P-T) boundary from five major terrestrial basins in the interior of the former Gondwana Supercontinent show large to very large (5 per mil-15 per mil) multiple negative spikes of δ13C, separated in places by sharp reversals of up to 20 per mil. Large oscillations of δ13Corg between -36 per mil and -15 per mil from mean values of ∼24±2 in India, ∼26±2 in Madagascar, and ∼23±2 in South Africa occur before and after the P-T transition. The mean values are within the range of modern C3 plants (∼-25 per mil). The negative δ13Corg spikes of the terrestrial plant remains complement similar spikes of smaller amplitude recorded globally in marine carbonates across the P-T boundary. Sensitivity analyses of carbon fluxes in a coupled atmosphere-ocean system indicate that the sharp declines in terrestrial and marine δ13C can be explained by episodic release of methane from clathrates (∼-60 per mil) either directly into the atmosphere or via the oceans, possibly during the disintegration of the southern continental shelf of Tethys. The rapid increases in δ13C may either signal aborted attempts of C4 plants (∼-13 per mil) to establish themselves at the expense of C3 plants or, more likely, reflect a punctuated increase in C3 biomass production related to elevated atmospheric CO2. Detection of a gradual negative trend in the Upper Permian and a similar positive recovery in the Lower Triassic, separated by up to three large negative δ13C spikes across the P-T boundary in at least four terrestrial sections, caution against models of the end-Paleozoic biodiversity collapse and ensuing Mesozoic recovery based on a singular perturbation at the P-T boundary. Rather, these transitions may reflect multiple ecosystem stability states and abrupt responses during gradual forcing of a complex nonlinear system with thresholds.

Africa, India and Madagascar were once part of the supercontinent of Gondwana. This land mass began to fragment approx. 170 million years ago, and by 83 million years, all of the major components we recognize today were separated by tracts of water. Madagascar’s fossil record and estimates of the timing of the extant vertebrate radiations in Madagascar are not easily reconciled with this history of fragmentation. Fossil faunas that lived prior to approx. 65 million years had a cosmopolitan flavour, but this was lost after the Cretaceous-Tertiary boundary. Phylogenetic reconstructions of most extant Malagasy vertebrate radiations indicate divergence times that postdate the End-Cretaceous (lemurs, tenrecs, cichlid fish) and even the Early Miocene (chameleons, carnivores, rodents). Most biogeographic explanations of these groups rely, therefore, on Simpson’s model of sweepstakes dispersal (see also cover figure), but there are significant problems in applying the model to migrations from Africa to Madagascar, although its application is not so intractable between India and Madagascar. Alternative migration routes for consideration lie: (1) along the suite of fracture zones between Antarctica and Africa/Madagascar (known as the Antarctic-Africa Corridor), which may have been exposed episodically above sea level; (2) along a series of submerged basaltic ridges/plateaus with known or suspected continental crust between Antarctica and Africa/Madagascar/India flanking the Antarctic-Africa Corridor (e.g. the Madagascar Ridge, Mozambique Ridge, Conrad Plateau, Gunnerus Ridge); (3) between Africa and Madagascar along the Davie Ridge (parts of which are known to have been exposed episodically above sea level); (4) along the Deccan hotspot corridor between India and greater Africa.

About 30% of the Earth is covered by continents, but only about 10 small kernels of these continentsae—known as Archaean cratonsae—are continental fragments formed before 2.5 Gyr ago. The Kaapvaal craton of South Africa, which formed and stabilized between 3.7 and 2.7 Gyr ago, is one of the oldest reasonably sized examples of these continental fragments. It consists of a mosaic of subdomains that have been welded together by processes similar to those of modern-day plate tectonics. The earliest subdomains may have owed their origin to the onset of efficient recycling from the Earth's hydrosphere into the mantle.

Aim: To investigate the validity of Simpson's model of sweepstakes dispersal, particularly as it applies to the colonization of Madagascar by African mammals. We chose lemurs as a classic case. Location: The East African coast, the Mozambique Channel and Madagascar. Methods: First, we investigated the assumptions underlying Simpson's statistical model as it relates to dispersal events. Second, we modelled the fate of a natural raft carrying one or several migrating mammals under a range of environmental conditions: in the absence of winds or currents, in the presence of winds and currents, and with and without a sail. Finally, we investigated the possibility of an animal being transported across the Mozambique Channel by an extreme climatic event like a tornado or a cyclone. Results: Our investigations show that Simpson's assumptions are consistently violated when applied to scenarios of over-water dispersal by mammals. We suggest that a simple binomial probability model is an inappropriate basis for extrapolating the likelihood of dispersal events. One possible alternative is to use a geometric probability model. Our estimates of current and wind trajectories show that the most likely fate for a raft emerging from an estuary on the east coast of Africa is to follow the Mozambique current and become beached back on the African coast. Given prevailing winds and currents, transport from Madagascar to Africa is very much more likely than the reverse process. Freak transport by means of a hurricane or tornado is even less likely than rafting for mammals. Main conclusions: Our models suggest that the scenario of sweepstakes dispersal that currently enjoys wide support is not valid at either the theoretical or the applied level when applied to the hypothetical invasion of Madagascar by African mammals. Alternative explanations should be sought.

Aim  We investigate the hypothesis that it was the capacity for torpor or hibernation that enabled the lemuriforms (and possibly other mammal groups, e.g. tenrecs and rodents) to invade Madagascar by means of over‐water dispersal. Location  Madagascar, East Africa and the Mozambique Channel. Methods  We consider the body weights and life‐style features of living primate taxa that employ heterothermy. Using this information as a standard for comparison, we summarize the available information on the Palaeogene strepsirrhine radiation (i.e. members of the infraorder Adapiformes, the extinct sister‐taxon to the lemuriforms, as well as putative stem lemuriforms), particularly with respect to possible trends in body weight among early, middle and late Eocene adapiforms. We discuss Eocene climatic conditions in the northern hemisphere and Africa, and assess the likelihood of adaptations for heterothermy in adapiforms. Finally, we estimate the body weights of the common ancestors to the living Lemuriformes and Lemuroidea using the method of phylogenetically independent contrasts. Results  The mean body weights estimated for the early, middle and late Eocene strepsirrhine faunas remain at approximately 2 kg, outside of the range of living primates using heterothermy. The adapiforms’ appearance coincided with the ‘initial Eocene thermal maximum’, an unusually hot period of global warming, and their demise corresponded with a major cooling event coincident with the appearance of ice sheets on Antarctica. They show no evidence of having evolved adaptations that allowed them to withstand climatic deterioration. The body weights of the ancestral lemuriform and ancestral lemuroid are of a similar order to the mean body weight estimated for the adapiforms, i.e. approximately 1.8 and 2.1 kg, respectively. Main conclusions  The available evidence argues against the widespread use of heterothermy by adapiforms. The adapiform–lemuriform divergence may have been the result of the lemuriforms adapting to the drier and more seasonal environments that characterized the African Eocene, and this suite of adaptations may have included the use of heterothermy, but there is as yet no substantial evidence to confirm the presence of either group on the continent prior to c. 40 Ma. The estimated body weights of the common lemuriform and lemuroid ancestors are well outside the size range of living mammals that employ heterothermy. We conclude that the hypothesis that it was the ability to use heterothermy that enabled the strepsirrhines, and not the haplorhines, to invade Madagascar, is unlikely. Alternative explanations for this anomaly should be sought.

Abstract Muscle fiber size and oxidative metabolism are inversely related, suggesting that a glycolytic metabolism may offer a growth advantage in muscle fibers. However, the mechanisms underlying this advantage remains unknown. Nearly 100 years ago, Warburg reported that cancer cells take up more glucose to produce glycolytic intermediates for anabolic reactions such as amino acid-protein synthesis. The aim of this study was to test whether glycolysis contributes to anabolic signalling responses and hypertrophy in post-mitotic muscle cells. Skeletal muscle hypertrophy was induced in vitro by treating mouse C2C12 myotubes with IGF-1. 14C glucose was added to differentiation medium and radioactivity in isolated protein was measured. We exposed differentiated C2C12 and primary mouse myotubes, to 2-deoxyglucose (2DG) and PHGDH siRNA upon which we assessed myotube diameter and signaling pathways involved in the regulation of muscle fiber size. Here, we present evidence that, hypertrophying C2C12 myotubes undergo a cancer-like metabolic reprogramming. First, IGF-1-induced C2C12 myotube hypertrophy increases shunting of carbon from glucose into protein. Second, reduction of glycolysis through 2-deoxy-D-glucose (2DG) lowers C2C12 and primary myotube size 16-40%. Third, reducing the cancer metabolism-associated enzyme PHGDH decreases C2C12 and primary myotube size 25-52%, whereas PHGDH overexpression increases C2C12 myotube size ≈20%. Fourth, the muscle hypertrophy-promoting kinase AKT regulates PHGDH expression. Together these results suggest that glycolysis is important for hypertrophying C2C12 myotubes by reprograming their metabolism similar to cancer cells. Competing Interest Statement The authors have declared no competing interest. Footnotes * ↵* Joint last authors. * 1 lianstadhouders{at}hotmail.com * 2 sander.verbrugge{at}tum.de * 4 jonathon.smith{at}ki.se * 3 brendan.gabriel1{at}abdn.ac.uk * 1 tim_hammersen05{at}hotmail.de * 5 detmar.kolijn{at}ruhr-uni-bochum.de * 1 ilsevogel{at}gmail.com * 6 a.mohamed.11{at}aberdeen.ac.uk * 1 g.m.j.de.wit{at}vu.nl * 1 c.offringa{at}vu.nl * 1 w.m.h.hoogaars{at}umcg.nl * 8 gehlert{at}uni-hildesheim.de * 2 henning.wackerhage{at}tum.de * 1 r.t.jaspers{at}vu.nl

This randomized, controlled trial evaluated AZD7442 (a combination of tixagevimab and cilgavimab, monoclonal antibodies targeting the SARS-CoV-2 spike protein) for the prevention of Covid-19 in adults at high risk for SARS-CoV-2 infection. AZD7442 was found to have approximately 77% efficacy in preventing symptomatic infection.