Upscaling nitrogen removal capacity from local hotspots to low stream orders’ drainage basins

International audienceDenitrification is the main process removing nitrate in river drainage basins and buffer input from agricultural land and limits aquatic ecosystem pollution. However, the identification of denitrification hotspots (for example, riparian zones), their role in a landscape context and the evolution oftheir overall removal capacity at the drainage basin scale are still challenging. The main approaches used (that is, mass balance method, denitrification proxies, and potential wetted areas) suffer from methodological drawbacks. We review these approaches and the key frameworks that have been proposed to date to formalize the understanding of the mechanisms driving denitrification: (i) Diffusion versus advection pathways of nitrate transfer, (ii) the biogeochemical hotspot, and (iii) the Damköhler ratio. Based on these frameworks, we propose to use high-resolution mapping of catchment topography and landscape pattern to define both potential denitrification sites and the dynamic hydrologic modeling at a similar spatial scale (<10 km2). It would allow the quantification of cumulative denitrification activity at the small catchment scale, using spatially distributed Damköhler and Peclet numbers and biogeochemical proxies. Integration of existing frameworks with new tools and methods offers the potential for significant breakthroughs in the quantification and modeling of denitrification in small drainage basins. This can provide a basis for improved protection and restoration of surface water and groundwater quality

Organizational Principles of Hyporheic Exchange Flow and Biogeochemical Cycling in River Networks Across Scales

Hyporheic zones increase freshwater ecosystem resilience to hydrological extremes and global environmental change. However, current conceptualizations of hyporheic exchange, residence time distributions, and the associated biogeochemical cycling in streambed sediments do not always accurately explain the hydrological and biogeochemical complexity observed in streams and rivers. Specifically, existing conceptual models insufficiently represent the coupled transport and reactivity along groundwater and surface water flow paths, the role of autochthonous organic matter in streambed biogeochemical functioning, and the feedbacks between surface-subsurface ecological processes, both within and across spatial and temporal scales. While simplified approaches to these issues are justifiable and necessary for transferability, the exclusion of important hyporheic processes from our conceptualizations can lead to erroneous conclusions and inadequate understanding and management of interconnected surface water and groundwater environments. This is particularly true at the landscape scale, where the organizational principles of spatio-temporal dynamics of hyporheic exchange flow (HEF) and biogeochemical processes remain largely uncharacterized. This article seeks to identify the most important drivers and controls of HEF and biogeochemical cycling based on a comprehensive synthesis of findings from a wide range of river systems. We use these observations to test current paradigms and conceptual models, discussing the interactions of local-to-regional hydrological, geomorphological, and ecological controls of hyporheic zone functioning. This improved conceptualization of the landscape organizational principles of drivers of HEF and biogeochemical processes from reach to catchment scales will inform future river research directions and watershed management strategies

Transient receptor potential canonical 4 and 5 proteins as targets in cancer therapeutics

Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca²+ entry because of the critical roles played by Ca²+ in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (−)-englerin A. We conclude that further research is both justified and necessary before these proteins can be considered as strong targets for anti-cancer cell drug discovery programmes. It is nevertheless already apparent that inhibitors of the channels would be unlikely to cause significant adverse effects, but, rather, have other effects which may be beneficial in the context of cancer and chemotherapy, potentially including suppression of innate fear, visceral pain and pathological cardiac remodelling

Increased circulation time of Plasmodium falciparum underlies persistent asymptomatic infection in the dry season

The dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquito vectors to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the human host or compromising host survival, is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5- to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of individuals with febrile malaria in the transmission season, coinciding with longer circulation within each replicative cycle of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication but rather to increased splenic clearance of longer-circulating infected erythrocytes, which likely maintain parasitemias below clinical and immunological radar. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence

Exploring decreased cytoadhesion in asymptomatic Plasmodium falciparum infections during the dry season

In many malaria endemic regions Plasmodium falciparum is seasonally transmitted, since parasite transmission is interrupted by the absence of anopheline mosquitoes during the dry season. P. falciparum persists at low parasitaemia during the dry season months through mechanisms involving longer time in circulation within each replicative cycle of infected erythrocytes without adhering to the endothelium, compared to clinical cases in the wet season. Cytoadhesion of infected erythocytes is mediated by parasite ligands trafficked via de-novo formed sorting organelles (Maurer’s cleft) to the surface of infected erythrocytes and anchored in knob structures. The adhesion ligands bind to endothelial cell receptors, sequestering infected erythrocytes in the vasculature and thus protecting parasites from splenic clearance. This thesis aimed to understand the mechanisms leading to decreased cytoadhesion of infected erythrocyte, as altered formation of knobs, impaired trafficking of adhesion molecules through the host iRBC, or reduced presentation of adhesion molecules on the iRBC surface, as well as the possible contribution of the host environment. Additionally, it investigates whether, as a consequence of deceased adhesion, the longer-circulationg iRBC are at higher risk of splenic clearance. To address this, we collected infected erythrocytes from asymptomatic individuals at the end of the dry season and from individuals at their first febrile malaria episode during the transmission season. Using an artificial spleen, we found that circulating iRBCs during the dry season are more efficiently filtered in the spleen. Erythrocyte remodeling and knob density were analyzed by transmission and scanning electron microscopy in developmental stage-matched samples from asymptomatic individuals at the end of the dry season and from individuals at their first febrile malaria episode during the transmission season. Knobs on the surface of the infected erythrocyte were detected at equal densities in both groups but with slightly smaller diameter in the dry season. Maurer’s clefts were formed in the host cells in all samples, but were found more frequently in infected erythrocytes in the dry season and were localized at slightly higher distance to the erythrocyte plasma membrane. However, the differences found were small and of unknown biological significance. Further, we quantified the transcription of parasite genes involved in host cell remodeling by qRT-PCR found differential expression of three genes coding for Maurer’s cleft proteins which are involved in adhesin trafficking, however possibly as a result of imperfect developmental stage matching. Hence, to test whether low parasite adhesion during the dry season stems from decreased expression of parasite ligands on the surface of erythrocytes, we used flow cytometry to compare the binding of hyperimmune plasma to the surface of P. falciparum-infected erythrocytes. We did not observe different labeling efficiencies in infected erythrocytes collected from asymptomatic individuals during the dry season vs. individuals presenting with acute febrile malaria during the rainy season. On the host side, we investigated how different inflammatory states in asymptomatic and clinical malaria cases alter the availability of host adhesion receptors on endothelial cells. Compared to plasmas from clinical malaria cases, we found lower levels of endothelium-stimulating cytokines and soluble adhesion receptors in plasmas of donors in the dry season, independent of if they carried asymptomatic P. falciparum infection or not. We explored whether this difference in endothelial receptor expression affected cytoadhesion efficiency, but in a preliminary test we found no differences in cytoadhesion of infected erythrocytes to endothelial cells stimulated with plasmas from donors with clinical malaria in the transmission season or asymptomatic donors or healthy controls in the dry season. In summary, the presence of only minor differences in the ultrastructure and no differential labeling by hyperimmune pooled plasma suggests that the contribution of altered host cell remodeling to decreased cytoadhesion in the dry season is only minimal. However, we have first indications that the host environment in the dry season provides less receptors for adhesion. Further, through more efficient splenic clearance of longer-circulating infected erythrocytes, parasitemias are maintained low in asymptomatic infections in the dry season, allowing P. falciparum to persist for several months

Binding brain better—matching var genes and endothelial receptors

Cerebral malaria remains a major cause of death for African children, and mechanistic insights regarding the establishment of brain pathology are greatly needed. Expression of specific domains of parasite's var genes promoting brain adhesion of infected erythrocytes had been previously identified, but binding specificities and the receptor preference in the brain endothelial cells had not been fully described. The study by Storm et al () in this issue of EMBO Molecular Medicine demonstrates that binding to brain endothelial cells via EPCR and ICAM‐1 is increased in parasites causing cerebral malaria compared to parasites causing uncomplicated malaria. Furthermore, expression levels of var genes encoding the CIDRα1 domain with EPCR affinity correlate with the receptor‐dependent binding to brain, but not dermal endothelial cells, highlighting the important role of EPCR in cerebral malaria pathology