Innate immune receptor NOD2 mediates LGR5+ intestinal stem cell protection against ROS cytotoxicity via mitophagy stimulation

International audienceThe nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist muramyl dipeptide (MDP), a peptidoglycan motif common to all bacteria, supports leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)+ intestinal stem cell (ISC) survival through NOD2 activation upon an otherwise lethal oxidative stress-mediated signal. However, the underlying protective mechanisms remain unknown. Here, using irradiation as stressor and primarily murine-derived intestinal organoids as a model system, we show that MDP induced a significant reduction of total and mitochondrial reactive oxygen species (ROS) within ISCs, which was associated with mitophagy induction. ATG16L1 knockout (KO) and NOD2 KO organoids did not benefit from the MDP-induced cytoprotection. We confirmed the MDP-dependent induction of ISC mitophagy upon stress in vivo. These findings elucidate the NOD2-mediated mechanism of cytoprotection involving the clearance of the lethal excess of ROS molecules through mitophagy, triggered by the coordinated activation of NOD2 and ATG16L1 by a nuclear factor κB (NF-κB)-independent pathway

Assessing Volcanic Controls on Miocene Climate Change

The Miocene period saw substantially warmer Earth surface temperatures than today, particularly during a period of global warming called the Mid Miocene Climatic Optimum (MMCO; ∼17–15 Ma). However, the long-term drivers of Miocene climate remain poorly understood. By using a new continuous climate-biogeochemical model (SCION), we can investigate the interaction between volcanism, climate and biogeochemical cycles through the Miocene. We identify high tectonic CO2 degassing rates and further emissions associated with the emplacement of the Columbia River Basalt Group as the primary driver of the background warmth and the MMCO respectively. We also find that enhanced weathering of the basaltic terrane and input of explosive volcanic ash to the oceans are not sufficient to drive the immediate cooling following the MMCO and suggest that another mechanism, perhaps the change in ocean chemistry due to massive evaporite deposition, was responsible

Transitions across Melancholia States in a climate model: reconciling the deterministic and stochastic points of view

The Earth is well known to be, in the current astronomical configuration, in a regime where two asymptotic states can be realized. The warm state we live in is in competition with the ice-covered snowball state. The bistability exists as a result of the positive ice-albedo feedback. In a previous investigation performed on a intermediate complexity climate model we identified the unstable climate states (melancholia states) separating the coexisting climates, and studied their dynamical and geometrical properties. The melancholia states are ice covered up to the midlatitudes and attract trajectories initialized on the basin boundary. In this Letter, we study how stochastically perturbing the parameter controlling the intensity of the incoming solar radiation impacts the stability of the climate. We detect transitions between the warm and the snowball state and analyze in detail the properties of the noise-induced escapes from the corresponding basins of attraction. We determine the most probable paths for the transitions and find evidence that the melancholia states act as gateways, similarly to saddle points in an energy landscape

Assessing Volcanic Controls on Miocene Climate Change

The Miocene period saw substantially warmer Earth surface temperatures than today, particularly during a period of global warming called the Mid Miocene Climatic Optimum (MMCO; ∼17–15 Ma). However, the long-term drivers of Miocene climate remain poorly understood. By using a new continuous climate-biogeochemical model (SCION), we can investigate the interaction between volcanism, climate and biogeochemical cycles through the Miocene. We identify high tectonic CO2 degassing rates and further emissions associated with the emplacement of the Columbia River Basalt Group as the primary driver of the background warmth and the MMCO respectively. We also find that enhanced weathering of the basaltic terrane and input of explosive volcanic ash to the oceans are not sufficient to drive the immediate cooling following the MMCO and suggest that another mechanism, perhaps the change in ocean chemistry due to massive evaporite deposition, was responsible

An early Cambrian greenhouse climate

The oceans of the early Cambrian (~541 to 509 million years ago) were the setting for a marked diversification of animal life. However, sea temperatures — a key component of the early Cambrian marine environment — remain unconstrained, in part because of a substantial time gap in the stable oxygen isotope (delta 18 O) record before the evolution of euconodonts. We show that previously overlooked sources of fossil biogenic phosphate have the potential to fill this gap. Pristine phosphatic microfossils from the Comley Limestones, UK, yield a robust delta 18 O signature, suggesting sea surface temperatures of 20° to 25°C at high southern paleolatitudes (~65°S to 70°S) between ~514 and 509 million years ago. These sea temperatures are consistent with the distribution of coeval evaporite and calcrete deposits, peak continental weathering rates, and also our climate model simulations for this interval. Our results support an early Cambrian greenhouse climate comparable to those of the late Mesozoic and early Cenozoic, offering a framework for exploring the interplay between biotic and environmental controls on Cambrian animal diversification

Nutrients as the dominant control on the spread of anoxia and euxinia across the Cenomanian-Turonian oceanic anoxic event (OAE2): Model-data comparison

International audienc

Investigating ocean deoxygenation during the PETM through the Cr isotopic signature of foraminifera

Over the past several decades, oxygen minimum zones have rapidly expanded due to rising temperatures raising concerns about the impacts of future climate change. One way to better understand the drivers behind this expansion is to evaluate the links between climate and seawater deoxygenation in the past especially in times of geologically abrupt climate change such as the Palaeocene-Eocene Thermal Maximum (PETM), a well characterised period of rapid warming ~56 million years ago. We have developed and applied the novel redox proxies of foraminiferal Cr isotopes(δ53Cr) and Ce anomalies (Ce/Ce*) to assess changes in paleo-redox conditions arising from changes in oxygen availability. Both δ53Cr and Cr concentrations decrease notably over the PETM at intermediate to upper abyssal water depths,indicative of widespread reductions in dissolved oxygen concentrations. An apparent correlation between the sizes of δ53Cr and benthic δ18O excursions during the PETM suggests temperature is one of the main controlling factors of deoxygenation in the open ocean. ODP Sites 1210 in the Pacific and 1263 in the Southeast Atlantic suggest that deoxygenation is associated with warming and circulation changes, as supported by Ce/Ce* data. Our geochemical data are supported by simulations from an intermediate complexity climate model (cGENIE), which show that during the PETM anoxia was mostly restricted to the Tethys Sea, while hypoxia was more widespread as a result of increasing atmospheric CO2 (from 1 to 6 times pre-industrial values)

Factors that inhibit snowball Earth simulation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94616/1/palo1176.pd

Orbitally forced ice sheet fluctuations during the Marinoan Snowball Earth glaciation

Two global glaciations occurred during the Neoproterozoic. Snowball Earth theory posits that these were terminated after millions of years of frigidity when initial warming from rising atmospheric CO2 concentrations was amplified by the reduction of ice cover and hence a reduction in planetary albedo. This scenario implies that most of the geological record of ice cover was deposited in a brief period of melt-back. However, deposits in low palaeo-latitudes show evidence of glacial–interglacial cycles. Here we analyse the sedimentology and oxygen and sulphur isotopic signatures of Marinoan Snowball glaciation deposits from Svalbard, in the Norwegian High Arctic. The deposits preserve a record of oscillations in glacier extent and hydrologic conditions under uniformly high atmospheric CO2 concentrations. We use simulations from a coupled three-dimensional ice sheet and atmospheric general circulation model to show that such oscillations can be explained by orbital forcing in the late stages of a Snowball glaciation. The simulations suggest that while atmospheric CO2 concentrations were rising, but not yet at the threshold required for complete melt-back, the ice sheets would have been sensitive to orbital forcing. We conclude that a similar dynamic can potentially explain the complex successions observed at other localities