Increased levels of calprotectin in obesity are related to macrophage content: impact on inflammation and effect of weight loss

Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage-related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity-associated comorbidities.     

Endophilin,Lamellipodin, and Mena cooperate to regulate F‐actin‐dependent EGF‐receptor endocytosis

The epidermal growth factor receptor (EGFR) plays an essential role during development and diseases including cancer. Lamellipodin (Lpd) is known to control lamellipodia protrusion by regulating actin filament elongation via Ena/VASP proteins. However, it is unknown whether this mechanism supports endocytosis of the EGFR. Here, we have identified a novel role for Lpd and Mena in clathrin‐mediated endocytosis (CME) of the EGFR. We have discovered that endogenous Lpd is in a complex with the EGFR and Lpd and Mena knockdown impairs EGFR endocytosis. Conversely, overexpressing Lpd substantially increases the EGFR uptake in an F‐actin‐dependent manner, suggesting that F‐actin polymerization is limiting for EGFR uptake. Furthermore, we found that Lpd directly interacts with endophilin, a BAR domain containing protein implicated in vesicle fission. We identified a role for endophilin in EGFR endocytosis, which is mediated by Lpd. Consistently, Lpd localizes to clathrin‐coated pits (CCPs) just before vesicle scission and regulates vesicle scission. Our findings suggest a novel mechanism in which Lpd mediates EGFR endocytosis via Mena downstream of endophilin.     

Palaeoenvironment and palaeoclimate of the Mousterian-Aurignacian transition in northern Iberia: the small-vertebrate assemblage from Cueva del Conde (Santo Adriano, Asturias)

The transition from the Middle Palaeolithic (Mousterian) to the Upper Palaeolithic (Aurignacian) has been one of the prominent themes in the archaeology of the European Palaeolithic for more than 20 years. One of the most controversial questions concerning this period is the extinction of the Neanderthals and their replacement by modern humans. In this context, Cueva del Conde, located in the northern part of the Iberian Peninsula, is an archaeo-palaeontological site that records the Mousterian to Aurignacian transition. It has been excavated since the beginning of the 20th century, first by the Conde de la Vega del Sella and systematically by a team from the University of Oviedo since 2001. Three main zones have been identified: the External Zone, dated to approximately 39 110 ± 520 BP (level N104); the Entrance Platform, dated between 38 250 ± 390 BP and 34 730 ± 500 BP; and Gallery A with a radiocarbon date of approximately 31 540 ± 400 BP (level N2a2). The small-vertebrate assemblages recovered from the water-screening of all sediment from the excavation campaigns represent at least 21 small mammal, amphibian and squamate taxa. The small-vertebrate associations in the three zones suggest a patchy landscape, dominated by humid meadows and woodland areas with the existence of water in the vicinity of the cave. The climate shows a more continental pattern during the Mousterian, though it was milder during the Aurignacian. The small vertebrates of the Cueva del Conde Mousterian and Aurignacian levels suggest a climate that differed from modern day temperatures, between −1.1 and −4.4 °C (mean annual temperature), placing these assemblages during Interstadials 9 to 7 (Is9 to 7).     

Colonization of Abandoned Land by Juniperus thurifera Is Mediated by the Interaction of a Diverse Dispersal Assemblage and Environmental Heterogeneity

Land abandonment is one of the most powerful global change drivers in developed countries where recent rural exodus has been the norm. Abandonment of traditional land use practices has permitted the colonization of these areas by shrub and tree species. For fleshy fruited species the colonization of new areas is determined by the dispersal assemblage composition and abundance. In this study we showed how the relative contribution to the dispersal process by each animal species is modulated by the environmental heterogeneity and ecosystem structure. This complex interaction caused differential patterns on the seed dispersal in both, landscape patches in which the process of colonization is acting nowadays and mature woodlands of Juniperus thurifera, a relict tree distributed in the western Mediterranean Basin. Thrushes (Turdus spp) and carnivores (red fox and stone marten) dispersed a high amount of seeds while rabbits and sheeps only a tiny fraction. Thrushes dispersed a significant amount of seeds in new colonization areas, however they were limited by the presence of high perches with big crop size. While carnivores dispersed seeds to all studied habitats, even in those patches where no trees of J. thurifera were present, turning out to be critical for primary colonization. The presence of Pinus and Quercus was related to a reduced consumption of J. thurifera seeds while the presence of fleshy fruited shrubs was related with higher content of J. thurifera seeds in dispersers’ faeces. Therefore environmental heterogeneity and ecosystem structure had a great influence on dispersers feeding behaviour, and should be considered in order to accurately describe the role of seed dispersal in ecological process, such as regeneration and colonization. J. thurifera expansion is not seed limited thanks to its diverse dispersal community, hence the conservation of all dispersers in an ecosystem enhance ecosystems services and resilience.