Knockout of receptor for advanced glycation end‐products attenuates age‐related renal lesions

Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE^?/? C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/g_food) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE^?/? mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE^?/? mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis (p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score (r = 0.92) was observed. Compared with old WT mice, old RAGE^?/? mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE^?/? mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE^?/? mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging.     

Structural and functional responses of invertebrate communities to climate change and flow regulation in alpine catchments

Understanding and predicting how biological communities respond to climate change is critical for assessing biodiversity vulnerability and guiding conservation efforts. Glacier‐ and snow‐fed rivers are one of the most sensitive ecosystems to climate change, and can provide early warning of wider‐scale changes. These rivers are frequently used for hydropower production but there is minimal understanding of how biological communities are influenced by climate change in a context of flow regulation. This study sheds light on this issue by disentangling structural (water temperature preference, taxonomic composition, alpha, beta and gamma diversities) and functional (functional traits, diversity, richness, evenness, dispersion and redundancy) effects of climate change in interaction with flow regulation in the Alps. For this, we compared environmental and aquatic invertebrate data collected in the 1970s and 2010s in regulated and unregulated alpine catchments. We hypothesized a replacement of cold‐adapted species by warming‐tolerant ones, high temporal and spatial turnover in taxa and trait composition, along with reduced taxonomic and functional diversities in consequence of climate change. We expected communities in regulated rivers to respond more drastically due to additive or synergistic effects between flow regulation and climate change. We found divergent structural but convergent functional responses between free‐flowing and regulated catchments. Although cold‐adapted taxa decreased in both of them, greater colonization and spread of thermophilic species was found in the free‐flowing one, resulting in higher spatial and temporal turnover. Since the 1970s, taxonomic diversity increased in the free flowing but decreased in the regulated catchment due to biotic homogenization. Colonization by taxa with new functional strategies (i.e. multivoltine taxa with small body size, resistance forms, aerial dispersion and reproduction by clutches) increased functional diversity but decreased functional redundancy through time. These functional changes could jeopardize the ability of aquatic communities facing intensification of ongoing climate change or new anthropogenic disturbances.     

Histamine releasing factor and elongation factor 1 alpha secreted via malaria parasites extracellular vesicles promote immune evasion by inhibiting specific T cell responses

Protozoan pathogens secrete nanosized particles called extracellular vesicles (EVs) to facilitate their survival and chronic infection. Here, we show the inhibition by Plasmodium berghei NK65 blood stage‐derived EVs of the proliferative response of CD4⁺ T cells in response to antigen presentation. Importantly, these results were confirmed in vivo by the capacity of EVs to diminish the ovalbumin‐specific delayed type hypersensitivity response. We identified two proteins associated with EVs, the histamine releasing factor (HRF) and the elongation factor 1α (EF‐1α) that were found to have immunosuppressive activities. Interestingly, in contrast to WT parasites, EVs from genetically HRF‐ and EF‐1α‐deficient parasites failed to inhibit T cell responses in vitro and in vivo. At the level of T cells, we demonstrated that EVs from WT parasites dephosphorylate key molecules (PLCγ1, Akt, and ERK) of the T cell receptor signalling cascade. Remarkably, immunisation with EF‐1α alone or in combination with HRF conferred a long‐lasting antiparasite protection and immune memory. In conclusion, we identified a new mechanism by which P. berghei‐derived EVs exert their immunosuppressive functions by altering T cell responses. The identification of two highly conserved immune suppressive factors offers new conceptual strategies to overcome EV‐mediated immune suppression in malaria‐infected individuals.     

Alpha and beta diversity of connected benthic–subsurface invertebrate communities respond to drying in dynamic river ecosystems

Drying disturbances are the primary determinant of aquatic community biodiversity in dynamic river ecosystems. Research exploring how communities respond to disturbance has focused on benthic invertebrates in surface sediments, inadequately representing a connected community that extends into the subsurface. We compared subsurface and benthic invertebrate responses to drying, to identify common and context‐dependent spatial patterns. We characterized community composition, alpha diversity and beta diversity across a gradient of drying duration. Subsurface communities responded to drying, but these responses were typically less pronounced than those of benthic communities. Despite compositional changes and in contrast to reductions in benthic alpha diversity, the alpha diversity of subsurface communities remained stable except at long drying durations. Some primarily benthic taxa were among those whose subsurface frequency and abundance responded positively to drying. Collectively, changing composition, stable richness and taxon‐specific increases in occurrence provide evidence that subsurface sediments can support persistence of invertebrate communities during drying disturbances. Beta‐diversity patterns varied and no consistent patterns distinguished the total diversity, turnover or nestedness of subsurface compared to benthic communities. In response to increasing drying duration, beta diversity increased or remained stable for benthic communities, but remained stable or decreased for subsurface communities, likely reflecting contrasts in the influence of mass effects, priority effects and environmental filtering. Dissimilarity between subsurface and benthic communities remained stable or increased with drying duration, suggesting that subsurface communities maintain distinct biodiversity value while also supporting temporary influxes of benthic taxa during drying events. As temporary rivers increase in extent due to global change, we highlight that recognizing the connected communities that extend into the subsurface sediments can enable holistic understanding of ecological responses to drying, the key determinant of biodiversity in these dynamic ecosystems.     

A two-site immunoradiometric assay of proatrial natriuretic factor. Application to tissue extracts

A "two-site" immunoradiometric assay (IRMA) was developed to specifically measure ANF (1-126), the precursor of ANF. This assay is based on the simultaneous use of antibodies against two different antigenic determinants: murine monoclonal antibody (2H2), which recognizes positions 101 through 103 of ANF, is linked to Immunobeads and employed to extract any ANF C-terminal; a second antibody, which is directed against positions 11 through 37, is radioiodinated and allows binding to any C-terminal-2H2-Immunobead material which bears the N-terminal antigenic site. A curvilinear relationship was obtained between radioactivity and the amount of proANF (1.5 to 400 fmol) added. Optimisation of IRMA was determined by the amount of 2H2-Immunobeads and labeled antibody used, incubation time as well as possible interference by both ANF (99-126) and ANF (1-98). Tissue extracts were used to validate the assay. proANF was detected in decreasing amounts in heart atria, heart ventricles, lungs, kidneys and adrenal glands. Its presence was further confirmed by reverse-phase HPLC followed by radioimmunoassay. IRMA is a simple and rapid method for the direct measurement of proANF in tissue extracts and chromatographic fractions. The presence of proANF in tissues strongly suggests local synthesis.     

Experimental evidence for a semi-flexible conformation for arabinoxylans

Purified water-soluble arabinoxylans from wheat flour were deferuloylated and fractionated into six fractions by graded ethanol precipitation. Further fractionation by HPSEC on Sephacryl S500 resulted in 48 subfractions with low polydispersity index. Conformational characteristics (persistence length q, hydrodynamic parameter v and Mark-Houwink exponent a) were similar among all subfractions and fitted with a semi-flexible conformation, whatever their structural characteristics. Substitution degree of the xylan backbone by arabinose residues has no influence on the conformation of arabinoxylans.