Summer soil drying exacerbated by earlier spring greening of northern vegetation

Earlier vegetation greening under climate change raises evapotranspiration and thus lowers spring soil moisture, yet the extent and magnitude of this water deficit persistence into the following summer remain elusive. We provide observational evidence that increased foliage cover over the Northern Hemisphere, during 1982–2011, triggers an additional soil moisture deficit that is further carried over into summer. Climate model simulations independently support this and attribute the driving process to be larger increases in evapotranspiration than in precipitation. This extra soil drying is projected to amplify the frequency and intensity of summer heatwaves. Most feedbacks operate locally, except for a notable teleconnection where extra moisture transpired over Europe is transported to central Siberia. Model results illustrate that this teleconnection offsets Siberian soil moisture losses from local spring greening. Our results highlight that climate change adaptation planning must account for the extra summer water and heatwave stress inherited from warming-induced earlier greening

Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis

The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells in vitro with defined ligands for toll-like receptor (TLR) 2 (lipoteichoic acid; LTA), TLR3 (polyIC), TLR4 (lipopolysaccharide; LPS), TLR5 (flagellin), and TLR9 (CpG-B). Supernatant fluids from the cultures were analyzed for levels of 5 different pro-inflammatory cytokines, interleukin (IL)-1\u3b2, IL-6, IL-8, IL-12p70, and TNF-\u3b1. After in vitro challenge with TLR ligands, PBC monocytes produced higher relative levels of pro-inflammatory cytokines, particularly IL-1\u3b2, IL-6, IL-8, and TNF-\u3b1, compared with controls. In conclusion, monocytes from patients with PBC appear more sensitive to signaling via select TLRs, resulting in secretion of selective pro-inflammatory cytokines integral to the inflammatory response that may be critical in the breakdown of self-tolerance. Copyrigh

Genetic polymorphisms of toll-like receptor 9 influence the immune response to CpG and contribute to hyper-IgM in primary biliary cirrhosis

The serum hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), found in 95% of patients. However, nearly every patient with PBC, including those who are AMA-negative, has an elevation in serum IgM. This hyper-IgM is neither representative of other Ig isoforms, nor is due to the levels of AMA. In fact, we have recently reported that the hyper-IgM is an innate immune response and can be induced with CpG-B with concurrent up-regulation of toll-like receptor 9 (TLR9). Based on these observations, we performed a two-tier study. First, we quantitated TLR9 genotypes in patients with PBC and controls and correlated these data with the B cell response to CpG-B. Second, based on these data, we performed an extensive TLR9 genotyping in a large cohort of patients and controls. We report herein that the 2848 AA TLR9 genotype is associated with enhanced gene expression and higher frequency of intracellular IgM+ B cells following CpG stimulation. Interestingly, however, despite the functional association, there is no difference in the distribution of TLR9 genotypes between patients and controls. Our data emphasize the importance of dissecting the innate immune response in PBC