Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire: an expert assessment

As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%–85% of permafrost carbon release can still be avoided if human emissions are actively reduced

Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease

Contains fulltext : 109047.pdf (publisher's version ) (Open Access)It is indispensable to thoroughly characterize each animal model in order to distinguish between primary and secondary effects of genetic changes. The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions. Nod1 and Nod2 are members of the Nucleotide-binding domain and Leucine-rich repeat containing Receptor (NLR) family. Several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2. These associations suggest that Nod1 and Nod2 play important roles in regulating the immune system.Three-month-old wildtype (Wt) and Nod1/2 DKO mice were sacrificed, body and organ weight were determined, and blood was drawn. Except for lower liver weight in Nod1/2 DKO mice, no differences were found in body/organ weight between both strains. Leukocyte count and composition was comparable. No significant changes in analyzed plasma biochemical markers were found. Additionally, intestinal and vascular permeability was determined. Nod1/2 DKO mice show increased susceptibility for intestinal permeability while vascular permeability was not affected. Next we induced septic shock and organ damage by administering LPS+PGN intraperitoneally to Wt and Nod1/2 DKO mice and sacrificed animals after 2 and 24 hours. The systemic inflammatory and metabolic response was comparable between both strains. However, renal response was different as indicated by partly preserved kidney function and tubular epithelial cell damage in Nod1/2 DKO at 24 hours. Remarkably, renal inflammatory mediators Tnfalpha, KC and Il-10 were significantly increased in Nod1/2 DKO compared with Wt mice at 2 hours.Systematic analysis of Nod1/2 DKO mice revealed a possible role of Nod1/2 in the development of renal disease during systemic inflammation

NOD2 3020insC mutation and the pathogenesis of Crohn's disease: impaired IL-1beta production points to a loss-of-function phenotype.

BACKGROUND: Mutations of the NOD2 gene increase the susceptibility of humans to Crohn's disease. NOD2 is a cytoplasmic receptor for the bacterial product peptidoglycan. There is considerable controversy in the literature whether the most common mutation in Crohn's disease, the 3020insC NOD2, leads to a loss of function, i.e. decreased cytokine production, or to the reverse, i.e. a gain of function. In previous papers we proposed the former, since we could show decreased cytokine production with a net proinflammatory status after exposure to muramyl dipeptide (MDP). METHODS: Because of recent data in the literature showing increased interleukin-beta (IL-1beta) production in mice with the corresponding NOD2 mutation, we investigated the production of this cytokine by cells of patients with Crohn's disease, either homozygous or heterozygous for the 3020insC mutation, and compared it with that of patients with Crohn's disease bearing the wild-type allele. RESULTS: A strongly decreased production of IL-1beta by peripheral mononuclear cells was found upon exposure to either peptidoglycan or peptidoglycan-derived MDP in homozygous patients bearing the 3020insC NOD2mutation. CONCLUSION: This sustains the hypothesis that the 3020insC mutation in the human NOD2 gene leads to a loss-of-function phenotype

Nucleotide-binding oligomerization domain-2 modulates specific TLR pathways for the induction of cytokine release.

Item does not contain fulltextThe recognition of peptidoglycan by cells of the innate immune system has been controversial; both TLR2 and nucleotide-binding oligomerization domain-2 (NOD2) have been implicated in this process. In the present study we demonstrate that although NOD2 is required for recognition of peptidoglycan, this leads to strong synergistic effects on TLR2-mediated production of both pro- and anti-inflammatory cytokines. Defective IL-10 production in patients with Crohn's disease bearing loss of function mutations of NOD2 may lead to overwhelming inflammation due to a subsequent Th1 bias. In addition to the potentiation of TLR2 effects, NOD2 is a modulator of signals transmitted through TLR4 and TLR3, but not through TLR5, TLR9, or TLR7. Thus, interaction between NOD2 and specific TLR pathways may represent an important modulatory mechanism of innate immune responses

Neutrophil Migration During Liver Injury Is Under Nucleotide-Binding Oligomerization Domain 1 Control

Background & Aims: A more complete understanding of the mechanisms involved in pathogen-associated molecular pattern signaling is crucial in the setting of liver injury. In intestinal diseases, nucleotide-binding oligomerization domain 1 (NOD1), a receptor for bacteria, appears to regulate cross-talk between innate and adaptive immunity, involving polymorphonuclear neutrophils (PMNs). Our aim was to explore the role of NOD1 in PMN-induced liver injury. Methods: Nod1+/+ and Nod1-/- mice were challenged with carbon tetrachloride (CCl4). Migration and phagocytosis of Nod1+/+ and Nod1-/- PMN were studied in vivo and ex vivo. We evaluated main inflammatory pathways in PMNs by Western blot and CD11b expression using fluorescence-activated cell sorting. Mice were submitted to liver ischemia/reperfusion. Results: After CCl4 exposure, livers of Nod1-/- mice had more than 50% less PMN infiltration within necrotic areas than those of Nod1+/+. PMNs isolated from Nod1-/- mice displayed a 90% decrease in migration capacity compared with Nod1+/+ PMNs, whereas FK 565, a potent NOD1 ligand, increased PMN migration. Upon FK 565 stimulation, mitogen-activated protein kinase and nuclear factor ?B were activated in Nod1+/+ PMNs, but less so in Nod1-/- PMNs. Expression of CD11b on the Nod1-/- PMN was decreased compared with Nod1+/+. The phagocytic capacity of Nod1-/- PMNs was decreased by more than 50% compared with Nod1+/+. In an ischemia/reperfusion model of PMN-induced liver injury, FK 565 increased lesions, whereas Nod1-/- mice were protected. Conclusions: The identification of NOD1 as a modulator of PMN function and migration in the liver suggests that this receptor may represent a new therapeutic target in PMN-dependent liver diseases. 2010 AGA Institute.SCOPUS: ar.jinfo:eu-repo/semantics/publishe