Host-microbe interaction in the gastrointestinal tract

The gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host-microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ-free mice, affecting the gut epithelium, immune system, and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ-free models. The application of cell-based in vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond. This article is protected by copyright. All rights reserved

Multi-modelling predictions show high uncertainty of required carbon input changes to reach a 4‰ target

Soils store vast amounts of carbon (C) on land, and increasing soil organic carbon (SOC) stocks in already managed soils such as croplands may be one way to remove C from the atmosphere, thereby limiting subsequent warming. The main objective of this study was to estimate the amount of additional C input needed to annually increase SOC stocks by 4%(0) at 16 long-term agricultural experiments in Europe, including exogenous organic matter (EOM) additions. We used an ensemble of six SOC models and ran them under two configurations: (1) with default parametrization and (2) with parameters calibrated site-by-site to fit the evolution of SOC stocks in the control treatments (without EOM). We compared model simulations and analysed the factors generating variability across models. The calibrated ensemble was able to reproduce the SOC stock evolution in the unfertilised control treatments. We found that, on average, the experimental sites needed an additional 1.5 +/- 1.2 Mg C ha(-)(1) year(-1) to increase SOC stocks by 4%(0) per year over 30 years, compared to the C input in the control treatments (multi-model median +/- median standard deviation across sites). That is, a 119% increase compared to the control. While mean annual temperature, initial SOC stocks and initial C input had a significant effect on the variability of the predicted C input in the default configuration (i.e., the relative standard deviation of the predicted C input from the mean), only water-related variables (i.e., mean annual precipitation and potential evapotranspiration) explained the divergence between models when calibrated. Our work highlights the challenge of increasing SOC stocks in agriculture and accentuates the need to increasingly lean on multi-model ensembles when predicting SOC stock trends and related processes. To increase the reliability of SOC models under future climate change, we suggest model developers to better constrain the effect of water-related variables on SOC decomposition

Modeling the effects of litter stoichiometry and soil mineral N availability on soil organic matter formation using CENTURY-CUE (v1.0)

Microbial decomposition of plant litter is a crucial process for the land carbon (C) cycle, as it directly controls the partitioning of litter C between CO2 released to the atmosphere versus the formation of new soil organic matter (SOM). Land surface models used to study the C cycle rarely considered flexibility in the decomposer C use efficiency (CUEd) defined by the fraction of decomposed litter C that is retained as SOM (as opposed to be respired). In this study, we adapted a conceptual formulation of CUEd based on assumption that litter decomposers optimally adjust their CUEd as a function of litter substrate C to nitrogen (N) stoichiometry to maximize their growth rates. This formulation was incorporated into the widely used CENTURY soil biogeochemical model and evaluated based on data from laboratory litter incubation experiments. Results indicated that the CENTURY model with new CUEd formulation was able to reproduce differences in respiration rate of litter with contrasting C&thinsp;:&thinsp;N ratios and under different levels of mineral N availability, whereas the default model with fixed CUEd could not. Using the model with flexible CUEd, we also illustrated that litter quality affected the long-term SOM formation. Litter with a small C&thinsp;:&thinsp;N ratio tended to form a larger SOM pool than litter with larger C&thinsp;:&thinsp;N ratios, as it could be more efficiently incorporated into SOM by microorganisms. This study provided a simple but effective formulation to quantify the effect of varying litter quality (N content) on SOM formation across temporal scales. Optimality theory appears to be suitable to predict complex processes of litter decomposition into soil C and to quantify how plant residues and manure can be harnessed to improve soil C sequestration for climate mitigation.</p

Spatial biases reduce the ability of Earth system models to simulate soil heterotrophic respiration fluxes

Heterotrophic respiration (Rh) is, at a global scale, one of the largest CO2 fluxes between the Earth's surface and atmosphere and may increase in the future. The previous generation of Earth system models (ESMs) was able to reproduce global fluxes relatively well, but at that, time no gridded products were available to perform an in-depth evaluation. The capacity of the new generation of ESMs used within the Coupled Model Intercomparison Project Phase 6 (CMIP6) to reproduce this flux has not been evaluated, meaning that the realism of resulting CO2 flux estimates is unclear. In this study, we combine recently released observational data on Rh and ESM simulations to evaluate the ability of 13 ESMs from CMIP6 to reproduce Rh. Only 4 of the 13 tested ESMs were able to reproduce the total Rh flux, but spatial analysis underlined important bias compensation for most of the ESMs, which generally showed an overestimation in tropical regions and an underestimation in arid regions. To identify the main drivers of the bias, we performed an analysis of the residuals and found that mean annual precipitation was the most important driver explaining the difference between ESM simulations and observation-derived products of Rh, with a higher bias between ESM simulations and Rh products where precipitation was high. Based on our results, next-generation ESMs should focus on improving the response of Rh to soil moisture.</p

Representation of dissolved organic carbon in the JULES land surface model (vn4.4_JULES-DOCM)

Current global models of the carbon (C) cycle consider only vertical gas exchanges between terrestrial or oceanic reservoirs and the atmosphere, thus not considering the lateral transport of carbon from the continents to the oceans. Therefore, those models implicitly consider all of the C which is not respired to the atmosphere to be stored on land and hence overestimate the land C sink capability. A model that represents the whole continuum from atmosphere to land and into the ocean would provide a better understanding of the Earth's C cycle and hence more reliable historical or future projections. A first and critical step in that direction is to include processes representing the production and export of dissolved organic carbon in soils. Here we present an original representation of dissolved organic C (DOC) processes in the Joint UK Land Environment Simulator (JULES-DOCM) that integrates a representation of DOC production in terrestrial ecosystems based on the incomplete decomposition of organic matter, DOC decomposition within the soil column, and DOC export to the river network via leaching. The model performance is evaluated in five specific sites for which observations of soil DOC concentration are available. Results show that the model is able to reproduce the DOC concentration and controlling processes, including leaching to the riverine system, which is fundamental for integrating terrestrial and aquatic ecosystems. Future work should include the fate of exported DOC in the river system as well as DIC and POC export from soil

Teaching molecular genetics: chapter 4—positional cloning of genetic disorders

Positional cloning is the approach of choice for the identification of genetic mutations underlying the pathological development of diseases with simple Mendelian inheritance. It consists of different consecutive steps, starting with recruitment of patients and DNA collection, that are critical to the overall process. A genetic analysis of the enrolled patients and their families is performed, based on genetic recombination frequencies generated by meiotic cross-overs and on genome-wide molecular studies, to define a critical DNA region of interest. This analysis culminates in a statistical estimate of the probability that disease features may segregate in the families independently or in association with specific molecular markers located in known regions. In this latter case, a marker can be defined as being linked to the disease manifestations. The genetic markers define an interval that is a function of their recombination frequencies with the disease, in which the disease gene is localised. The identification and characterisation of chromosome abnormalities as translocations, deletions and duplications by classical cytogenetic methods or by the newly developed microarray-based comparative genomic hybridisation (array CGH) technique may define extensions and borders of the genomic regions involved. The step following the definition of a critical genomic region is the identification of candidate genes that is based on the analysis of available databases from genome browsers. Positional cloning culminates in the identification of the causative gene mutation, and the definition of its functional role in the pathogenesis of the disorder, by the use of cell-based or animal-based experiments. More often, positional cloning ends with the generation of mice with homologous mutations reproducing the human clinical phenotype. Altogether, positional cloning has represented a fundamental step in the research on genetic renal disorders, leading to the definition of several disease mechanisms and allowing a proper diagnostic approach to many conditions

Lowering water table reduces carbon sink strength and carbon stocks in northern peatlands

Peatlands at high latitudes have accumulated >400 Pg carbon (C) because saturated soil and cold temperatures suppress C decomposition. This substantial amount of C in Arctic and Boreal peatlands is potentially subject to increased decomposition if the water table (WT) decreases due to climate change, including permafrost thaw-related drying. Here, we optimize a version of the Organizing Carbon and Hydrology In Dynamic Ecosystems model (ORCHIDEE-PCH4) using site-specific observations to investigate changes in CO2 and CH4 fluxes as well as C stock responses to an experimentally manipulated decrease of WT at six northern peatlands. The unmanipulated control peatlands, with the WT 2 kg C m−2 over 100 years when WT is lowered by 50 cm, while permafrost peatlands temporally switched from C sinks to sources. These results highlight that reductions in C storage capacity in response to drying of northern peatlands are offset in part by reduced CH4 emissions, thus slightly reducing the positive carbon climate feedbacks of peatlands under a warmer and drier future climate scenario

ORCHIDEE-PEAT (revision 4596), a model for northern peatland CO2, water, and energy fluxes on daily to annual scales

Peatlands store substantial amounts of carbon and are vulnerable to climate change. We present a modified version of the Organising Carbon and Hydrology In Dynamic Ecosystems (ORCHIDEE) land surface model for simulating the hydrology, surface energy, and CO2 fluxes of peatlands on daily to annual timescales. The model includes a separate soil tile in each 0.5 degrees grid cell, defined from a global peatland map and identified with peat-specific soil hydraulic properties. Runoff from non-peat vegetation within a grid cell containing a fraction of peat is routed to this peat soil tile, which maintains shallow water tables. The water table position separates oxic from anoxic decomposition. The model was evaluated against eddy-covariance (EC) observations from 30 northern peatland sites, with the maximum rate of carboxylation (V-cmax) being optimized at each site. Regarding short-term day-to-day variations, the model performance was good for gross primary production (GPP) (r(2) = 0.76; Nash-Sutcliffe modeling efficiency, MEF = 0.76) and ecosystem respiration (ER, r(2) = 0.78, MEF = 0.75), with lesser accuracy for latent heat fluxes (LE, r(2) = 0.42, MEF = 0.14) and and net ecosystem CO2 exchange (NEE, r(2) = 0.38, MEF = 0.26). Seasonal variations in GPP, ER, NEE, and energy fluxes on monthly scales showed moderate to high r(2) values (0.57-0.86). For spatial across-site gradients of annual mean GPP, ER, NEE, and LE, r(2) values of 0.93, 0.89, 0.27, and 0.71 were achieved, respectively. Water table (WT) variation was not well predicted (r(2) <0.1), likely due to the uncertain water input to the peat from surrounding areas. However, the poor performance of WT simulation did not greatly affect predictions of ER and NEE. We found a significant relationship between optimized V-cmax and latitude (temperature), which better reflects the spatial gradients of annual NEE than using an average V-cmax value.Peer reviewe

Ensemble modelling, uncertainty and robust predictions of organic carbon in long-term bare-fallow soils

ACKNOWLEDGEMENTS This study was supported by the project “C and N models inter-comparison and improvement to assess management options for GHG mitigation in agro-systems worldwide” (CN-MIP, 2014- 2017), which received funding by a multi-partner call on agricultural greenhouse gas research of the Joint Programming Initiative ‘FACCE’ through national financing bodies. S. Recous, R. Farina, L. Brilli, G. Bellocchi and L. Bechini received mobility funding by way of the French Italian GALILEO programme (CLIMSOC project). The authors acknowledge particularly the data holders for the Long Term Bare-Fallows, who made their data available and provided additional information on the sites: V. Romanenkov, B.T. Christensen, T. Kätterer, S. Houot, F. van Oort, A. Mc Donald, as well as P. Barré. The input of B. Guenet and C. Chenu contributes to the ANR “Investissements d’avenir” programme with the reference CLAND ANR-16-CONV-0003. The input of P. Smith and C. Chenu contributes to the CIRCASA project, which received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no 774378 and the projects: DEVIL (NE/M021327/1) and Soils‐R‐GRREAT (NE/P019455/1). The input of B. Grant and W. Smith was funded by Science and Technology Branch, Agriculture and Agri-Food Canada, under the scope of project J-001793. The input of A. Taghizadeh-Toosi was funded by Ministry of Environment and Food of Denmark as part of the SINKS2 project. The input of M. Abdalla contributes to the SUPER-G project, which received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no 774124.Peer reviewedPostprin

Two Genetic Determinants Acquired Late in Mus Evolution Regulate the Inclusion of Exon 5, which Alters Mouse APOBEC3 Translation Efficiency

Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 (mA3), an intracellular antiviral factor, has 2 allelic variations that are linked with different susceptibilities to beta- and gammaretrovirus infections among various mouse strains. In virus-resistant C57BL/6 (B6) mice, mA3 transcripts are more abundant than those in susceptible BALB/c mice both in the spleen and bone marrow. These strains of mice also express mA3 transcripts with different splicing patterns: B6 mice preferentially express exon 5-deficient (Δ5) mA3 mRNA, while BALB/c mice produce exon 5-containing full-length mA3 mRNA as the major transcript. Although the protein product of the Δ5 mRNA exerts stronger antiretroviral activities than the full-length protein, how exon 5 affects mA3 antiviral activity, as well as the genetic mechanisms regulating exon 5 inclusion into the mA3 transcripts, remains largely uncharacterized. Here we show that mA3 exon 5 is indeed a functional element that influences protein synthesis at a post-transcriptional level. We further employed in vitro splicing assays using genomic DNA clones to identify two critical polymorphisms affecting the inclusion of exon 5 into mA3 transcripts: the number of TCCT repeats upstream of exon 5 and the single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary. Distribution of the above polymorphisms among different Mus species indicates that the inclusion of exon 5 into mA3 mRNA is a relatively recent event in the evolution of mice. The widespread geographic distribution of this exon 5-including genetic variant suggests that in some Mus populations the cost of maintaining an effective but mutagenic enzyme may outweigh its antiviral function