Stable climate and surface mass balance in Svalbard over 1979–2013 despite the Arctic warming

With the help of the regional climate model MAR (Modèle Atmosphérique Régional) forced by the ERA-Interim reanalysis (MARERA) and the MIROC5 (Model for Interdisciplinary Research on Climate) global model (MARMIROC5) from the CMIP5 (Coupled Model Intercomparison Project) database, we have modelled the climate and surface mass balance of Svalbard at a 10 km resolution over 1979–2013. The integrated total surface mass balance (SMB) over Svalbard modelled by MARERA is negative (−1.6 Gt yr−1) with a large interannual variability (7.1 Gt) but, unlike over Greenland, there has been no acceleration of the surface melt over the past 35 years because of the recent change in atmospheric circulation bringing northwesterly flows in summer over Svalbard, contrasting the recent observed Arctic warming. However, in 2013, the atmospheric circulation changed to a south–southwesterly flow over Svalbard causing record melt, SMB (−20.4 Gt yr−1) and summer temperature. MIROC5 is significantly colder than ERA-Interim over 1980–2005 but MARMIROC5 is able to improve the near-surface MIROC5 results by simulating not significant SMB differences with MARERA over 1980–2005. On the other hand, MIROC5 does not represent the recent atmospheric circulation shift in summer and induces in MARMIROC5 a significant trend of decreasing SMB (−0.6 Gt yr−2) over 1980–2005

Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis.

It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2

Digging deeper into lymphatic vessel formation in vitro and in vivo

Background Abnormal lymphatic vessel formation (lymphangiogenesis) is associated with different pathologies such as cancer, lymphedema, psoriasis and graft rejection. Lymphatic vasculature displays distinctive features than blood vasculature, and mechanisms underlying the formation of new lymphatic vessels during physiological and pathological processes are still poorly documented. Most studies on lymphatic vessel formation are focused on organism development rather than lymphangiogenic events occurring in adults. We have here studied lymphatic vessel formation in two in vivo models of pathological lymphangiogenesis (corneal assay and lymphangioma). These data have been confronted to those generated in the recently set up in vitro model of lymphatic ring assay. Ultrastructural analyses through Transmission Electron Microscopy (TEM) were performed to investigate tube morphogenesis, an important differentiating process observed during endothelial cell organization into capillary structures

Modeling pre-metastatic lymphvascular niche in the mouse ear sponge assay.

Lymphangiogenesis, the formation of new lymphatic vessels, occurs in primary tumors and in draining lymph nodes leading to pre-metastatic niche formation. Reliable in vivo models are becoming instrumental for investigating alterations occurring in lymph nodes before tumor cell arrival. In this study, we demonstrate that B16F10 melanoma cell encapsulation in a biomaterial, and implantation in the mouse ear, prevents their rapid lymphatic spread observed when cells are directly injected in the ear. Vascular remodeling in lymph nodes was detected two weeks after sponge implantation, while their colonization by tumor cells occurred two weeks later. In this model, a huge lymphangiogenic response was induced in primary tumors and in pre-metastatic and metastatic lymph nodes. In control lymph nodes, lymphatic vessels were confined to the cortex. In contrast, an enlargement and expansion of lymphatic vessels towards paracortical and medullar areas occurred in pre-metastatic lymph nodes. We designed an original computerized-assisted quantification method to examine the lymphatic vessel structure and the spatial distribution. This new reliable and accurate model is suitable for in vivo studies of lymphangiogenesis, holds promise for unraveling the mechanisms underlying lymphatic metastases and pre-metastatic niche formation in lymph nodes, and will provide new tools for drug testing

Soluble factors regulated by epithelial-mesenchymal transition mediate tumour angiogenesis and myeloid cell recruitment.

peer reviewedEpithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been extensively studied, the impact of EMT on the crosstalk between tumor cells and the tumor microenvironment remains elusive. We aimed to identify EMT-regulated soluble factors that facilitate the recruitment of host cells in the tumor. Our findings indicate that EMT phenotypes relate to the induction of a panel of secreted mediators, namely IL-8, IL-6, sICAM-1, PAI-1 and GM-CSF, and implicate the EMT-transcription factor Snail as a regulator of this process. We further show that EMT-derived soluble factors are pro-angiogenic in vivo (in the mouse ear sponge assay), ex vivo (in the rat aortic ring assay) and in vitro (in a chemotaxis assay). Additionally, conditioned medium from EMT-positive cells stimulates the recruitment of myeloid cells. In a bank of 40 triple-negative breast cancers, tumors presenting features of EMT were significantly more angiogenic and infiltrated by a higher quantity of myeloid cells compared to tumors with little or no EMT. Taken together, our results show that EMT programs trigger the expression of soluble mediators in cancer cells that stimulate angiogenesis and recruit myeloid cells in vivo, which might in turn favor cancer spread

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: diagnostic and mechanistic relevance

Background & Aims: Serum microRNAs (miRNAs) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 NAFLD cases representing the complete NAFLD spectrum and 10 population controls). MiRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional NAFLD cases and 15 population controls by quantitative reverse transcriptase-polymerase chain reaction.Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages but miR-193a-5p consistently the showed increased levels in all comparisons. Relative to NAFL/NASH with mild fibrosis (stage 0/1), three miRNAs (miR-193a-5p, miR-378d and miR378d) were increased in cases with NASH and clinically significant fibrosis (stage 2-4), seven (miR193a-5p, miR-378d, miR-378e, miR-320b, c, d & e) increased in cases with NAFLD Activity Score (NAS) 5-8 compared with lower NAS, and three (miR-193a-5p, miR-378d, miR-378e) increased but one (miR-19b-3p) decreased in steatosis, activity, and fibrosis "activity" (SAF-A) score 2-4 compared with lower SAF-A. The significant findings for miR-193a-5p were replicated in the additional NAFLD cohort. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n=80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD

Evaluation des modèles climatiques régionaux MAR et WRF sur le Svalbard

Il est bien connu que les zones de hautes latitudes sont très sensibles aux changements climatiques. A cause du réchauffement global, la fonte des calottes a augmenté, ce qui à son tour a une influence sur le climat via des modifications de la circulation thermohaline, la rétroaction de l’albédo de la glace, l’augmentation du niveau des mers… Nous avons comparé le climat du Svalbard modélisé par deux modèles régionaux (MAR et WRF) à une résolution de 10 km sur la période 2000-2010 à des mesures provenant de plusieurs stations météorologiques localisées dans différentes régions de l’archipel afin d'évaluer lequel de ces modèles pouvait représenter au mieux le climat du Svalbard

Future climate and surface mass balance of Svalbard glaciers in an RCP8.5 climate scenario: a study with the regional climate model MAR forced by MIROC5

We simulated the 21st century Svalbard SMB with the regional model MAR (RCP8.5 scenario). Melt is projected to increase gently up to 2050 and then dramatically increase, with a larger increase in the south of the archipelago. This difference is due to larger ice albedo decrease in the south causing larger increase of absorbed solar radiation. The ablation area is projected to disappear over the entire Svalbard by 2085. The SMB decrease compared to present is projected to contribute 7mm to SLR

Evaluation of the regional climate model WRF over Svalbard

It is well known that high latitude zones are very sensitive to climate change. As a result of global warming, ice sheet melting has increased which in turn has an influence on climate through modifications of the thermohaline circulation, feedback of ice albedo, sea level rise, … Svalbard is an archipelago between 74 and 81°lat N and 60 percent of its area (62 248 km2) is covered with glaciers and ice sheets. The impact of global warming on the Svalbard cryosphere can be estimated with climate models. However, we need to use regional climate models as they offer the possibility of a higher resolution than general circulation models. We have ran two regional climate models (MAR and WRF) at a 10-kilometre resolution between 2006 and 2010 over Svalbard and compared their simulated climate to near surface measurements at several weather stations through the archipelago in order to determine which one of them could best represent the Svalbard climate

Current and future atmospheric circulation at 500 hPa over Greenland simulated by the CMIP3 and CMIP5 global models

The Greenland ice sheet is projected to be strongly affected by global warming. These projections are either issued from downscaling methods (such as Regional Climate Models) or they come directly from General Circulation Models (GCMs). In this context, it is necessary to evaluate the accuracy of the daily atmospheric circulation simulated by the GCMs, since it is used as forcing for downscaling methods. Thus, we use an automatic circulation type classification based on two indices (Euclidean distance and Spearman rank correlation using the daily 500 hPa geopotential height) to evaluate the ability of the GCMs from both CMIP3 and CMIP5 databases to simulate the main circulation types over Greenland during summer. For each circulation type, the GCMs are compared to three reanalysis datasets on the basis of their frequency and persistence differences. For the current climate (1961–1990), we show that most of the GCMs do not reproduce the expected frequency and the persistence of the circulation types and that they simulate poorly the observed daily variability of the general circulation. Only a few GCMs can be used as reliable forcings for downscaling methods over Greenland. Finally, when applying the same approach to the future projections of the GCMs, no significant change in the atmospheric circulation over Greenland is detected, besides a generalised increase of the geopotential height due to a uniform warming of the atmosphere