Dynamics of the terrestrial biosphere, climate and atmospheric CO₂ concentration during interglacials: a comparison between Eemian and Holocene

A complex earth system model (atmosphere and ocean general circulation models, ocean biogeochemistry and terrestrial biosphere) was used to perform transient simulations of two interglacial sections (Eemian, 128&ndash;113 ky B.P., and Holocene, 9 ky B.P.&ndash;present). The changes in terrestrial carbon storage during these interglacials were studied with respect to changes in the earth&apos;s orbit. The effects of different climate factors on changes in carbon storage were studied in offline experiments in which the vegetation model was forced only with temperature, hydrological parameters, radiation, or CO₂ concentration from the transient runs. <br><br> The largest anomalies in terrestrial carbon storage were caused by temperature changes. However, the increase in storage due to forest expansion and increased photosynthesis in the high latitudes was nearly balanced by the decrease due to increased respiration. Large positive effects on carbon storage were caused by an enhanced monsoon circulation in the subtropics between 128 and 121 ky B.P. and between 9 and 6 ky B.P., and by increases in incoming radiation during summer for 45&deg; to 70&deg; N compared to a control simulation with present-day insolation. <br><br> Compared to this control simulation, the net effect of these changes was a positive carbon storage anomaly in the terrestrial biosphere of about 200 Pg C for 125 ky B.P. and 7 ky B.P., and a negative anomaly around 150 Pg C for 116 ky B.P. Although the net increases for Eemian and Holocene were rather similar, the magnitudes of the processes causing these effects were different. The decrease in terrestrial carbon storage during the experiments was the main driver of an increase in atmospheric CO₂ concentration during both the Eemian and the Holocene

Changes in terrestrial carbon storage during interglacials: a comparison between Eemian and Holocene

International audienceA complex earth system model (atmosphere and ocean general circulation models, ocean biogeochemistry and terrestrial biosphere) was used to perform transient simulations of two interglacial sections (Eemian, 128?113 ky B.P., and Holocene, 9 ky B.P.-present). The changes in terrestrial carbon storage during these interglacials were studied with respect to changes in the earth's orbit. The effect of different climate factors for the changes in carbon storage were studied in offline experiments in which the vegetation model was forced with only temperature, hydrological parameters, radiation, or CO2 concentration from the transient runs. Although temperature caused the largest anomalies in terrestrial carbon storage, the increase in storage due to forest expansion and increased photosynthesis in the high latitudes was nearly balanced by the decrease due to increased respiration. Large positive effects on carbon storage came from an enhanced monsoon circulation in the subtropics between 128 and 121 ky B.P. and between 9 and 6 ky B.P., and from increases in incoming radiation during summer for 45° to 70° N compared to a control run with present-day insolation. Compared to this control run, the net effect of these changes was a positive carbon storage anomaly of about 200 Pg C for 125 ky B.P. and 7 ky B.P., and a negative anomaly around 150 Pg C for 116 ky B.P. Although the net increases for Eemian and Holocene were rather similar, the causes of this differ substantially. The decrease in terrestrial carbon storage during the experiments was the main driver of an increase in atmospheric CO2 concentration for both the Eemian and the Holocene

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Spinal codes

Spinal codes are a new class of rateless codes that enable wireless networks to cope with time-varying channel conditions in a natural way, without requiring any explicit bit rate selection. The key idea in the code is the sequential application of a pseudo-random hash function to the message bits to produce a sequence of coded symbols for transmission. This encoding ensures that two input messages that differ in even one bit lead to very different coded sequences after the point at which they differ, providing good resilience to noise and bit errors. To decode spinal codes, this paper develops an approximate maximum-likelihood decoder, called the bubble decoder, which runs in time polynomial in the message size and achieves the Shannon capacity over both additive white Gaussian noise (AWGN) and binary symmetric channel (BSC) models. Experimental results obtained from a software implementation of a linear-time decoder show that spinal codes achieve higher throughput than fixed-rate LDPC codes, rateless Raptor codes, and the layered rateless coding approach of Strider, across a range of channel conditions and message sizes. An early hardware prototype that can decode at 10 Mbits/s in FPGA demonstrates that spinal codes are a practical construction.Massachusetts Institute of Technology (Irwin and Joan Jacobs Presidential Fellowship)Massachusetts Institute of Technology (Claude E. Shannon Assistantship)Intel Corporation (Intel Fellowship

Vitamin K Antagonists, Non-Vitamin K Antagonist Oral Anticoagulants, and Vascular Calcification in Patients with Atrial Fibrillation

Background  Vitamin K antagonists (VKAs) are associated with coronary artery calcification in low-risk populations, but their effect on calcification of large arteries remains uncertain. The effect of non-vitamin K antagonist oral anticoagulants (NOACs) on vascular calcification is unknown. We investigated the influence of use of VKA and NOAC on calcification of the aorta and aortic valve. Methods  In patients with atrial fibrillation without a history of major adverse cardiac or cerebrovascular events who underwent computed tomographic angiography, the presence of ascending aorta calcification (AsAC), descending aorta calcification (DAC), and aortic valve calcification (AVC) was determined. Confounders for VKA/NOAC treatment were identified and propensity score adjusted logistic regression explored the association between treatment and calcification (Agatston score > 0). AsAC, DAC, and AVC differences were assessed in propensity score-matched groups. Results  Of 236 patients (33% female, age: 58 ± 9 years), 71 (30%) used VKA (median duration: 122 weeks) and 79 (34%) used NOAC (median duration: 16 weeks). Propensity score-adjusted logistic regression revealed that use of VKA was significantly associated with AsAC (odds ratio [OR]: 2.31; 95% confidence interval [CI]: 1.16-4.59; p  = 0.017) and DAC (OR: 2.38; 95% CI: 1.22-4.67; p  = 0.012) and a trend in AVC (OR: 1.92; 95% CI: 0.98-3.80; p  = 0.059) compared with non-anticoagulation. This association was absent in NOAC versus non-anticoagulant (AsAC OR: 0.51; 95% CI: 0.21-1.21; p  = 0.127; DAC OR: 0.80; 95% CI: 0.36-1.76; p  = 0.577; AVC OR: 0.62; 95% CI: 0.27-1.40; p  = 0.248). A total of 178 patients were propensity score matched in three pairwise comparisons. Again, use of VKA was associated with DAC ( p  = 0.043) and a trend toward more AsAC ( p  = 0.059), while use of NOAC was not (AsAC p  = 0.264; DAC p  = 0.154; AVC p  = 0.280). Conclusion  This cross-sectional study shows that use of VKA seems to contribute to vascular calcification. The calcification effect was not observed in NOAC users

Calcific aortic valve stenosis:hard disease in the heart: A biomolecular approach towards diagnosis and treatment

Calcific aortic valve stenosis (CAVS) is common in the ageing population and set to become an increasing economic and health burden. Once present, it inevitably progresses and has a poor prognosis in symptomatic patients. No medical therapies are proven to be effective in holding or reducing disease progression. Therefore, aortic valve replacement remains the only available treatment option. Improved knowledge of the mechanisms underlying disease progression has provided us with insights that CAVS is not a passive disease. Rather, CAVS is regulated by numerous mechanisms with a key role for calcification. Aortic valve calcification (AVC) is actively regulated involving cellular and humoral factors that may offer targets for diagnosis and intervention. The discovery that the vitamin K-dependent proteins are involved in the inhibition of AVC has boosted our mechanistic understanding of this process and has opened up novel avenues in disease exploration. This review discusses processes involved in CAVS progression, with an emphasis on recent insights into calcification, methods for imaging calcification activity, and potential therapeutic options

DEFICIENCY OF MYELOID PHD PROTEINS AGGRAVATES ATHEROGENESIS VIA MACROPHAGE APOPTOSIS AND PARACRINE FIBROTIC SIGNALING Atherogenic effects of myeloid PHD knockdown

AIMS: Atherosclerotic plaque hypoxia is detrimental for macrophage function. Prolyl hydroxylases (PHDs) initiate cellular hypoxic responses, possibly influencing macrophage function in plaque hypoxia. Thus, we aimed to elucidate the role of myeloid PHDs in atherosclerosis. METHODS AND RESULTS: Myeloid-specific PHD knockout (PHDko) mice were obtained via bone marrow transplantation (PHD1ko, PHD3ko) or conditional knockdown through lysozyme M-driven Cre recombinase (PHD2cko). Mice were fed high cholesterol diet for 6–12 weeks to induce atherosclerosis. Aortic root plaque size was significantly augmented 2.6-fold in PHD2cko, and 1.4-fold in PHD3ko compared to controls but was unchanged in PHD1ko mice. Macrophage apoptosis was promoted in PHD2cko and PHD3ko mice in vitro and in vivo, via the hypoxia-inducible factor (HIF) 1α/BNIP3 axis. Bulk and single-cell RNA data of PHD2cko bone marrow-derived macrophages (BMDMs) and plaque macrophages, respectively, showed enhanced HIF1α/BNIP3 signalling, which was validated in vitro by siRNA silencing. Human plaque BNIP3 mRNA was positively associated with plaque necrotic core size, suggesting similar pro-apoptotic effects in human. Furthermore, PHD2cko plaques displayed enhanced fibrosis, while macrophage collagen breakdown by matrix metalloproteinases, collagen production, and proliferation were unaltered. Instead, PHD2cko BMDMs enhanced fibroblast collagen secretion in a paracrine manner. In silico analysis of macrophage-fibroblast communication predicted SPP1 (osteopontin) signalling as regulator, which was corroborated by enhanced plaque SPP1 protein in vivo. Increased SPP1 mRNA expression upon PHD2cko was preferentially observed in foamy plaque macrophages expressing ‘triggering receptor expressed on myeloid cells-2’ (TREM2hi) evidenced by single-cell RNA, but not in neutrophils. This confirmed enhanced fibrotic signalling by PHD2cko macrophages to fibroblasts, in vitro as well as in vivo. CONCLUSION: Myeloid PHD2cko and PHD3ko enhanced atherosclerotic plaque growth and macrophage apoptosis, while PHD2cko macrophages further activated collagen secretion by fibroblasts in vitro, likely via paracrine SPP1 signalling through TREM2hi macrophages